Graeme Cottrell

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+44 (0) 118 378 7027
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Associate Professor
- Director of Postgraduate Progression
- School Director of Postgraduate Research Studies
Areas of interest
My research is focused on understanding the role of peptidases and neuropeptides in the trafficking and signaling of receptors and ion channels expressed in the cardiovascular and nervous systems. The objective is to understand the molecular and cellular basis of mechanisms that regulate the signal transduction evoked by cell-surface receptors and ion channels and how dysregulation of these mechanisms can lead to pathological conditions and cause disease.
Proteolysis and Disease
My interest in peptidases and proteolytic processes started during my Ph.D. at the University of Leeds. When I moved to the University of California, San Francisco, to work as post-doctoral fellow I then became interested in the physiological and pathophysiological roles of proteolysis. Protease-activated receptors (PARs) are a sub-family of G protein-coupled receptors (GPCRs) that are activated by the proteolytic action of certain peptidases. I was the first to show that trypsin IV was co-expressed with PAR2 in epithelial cells of the prostate, colon, and airway and in human colonic mucosa and can signal to these cells by cleaving PAR21. Trypsin IV is an inhibitor-resistant form of trypsin, and can signal through PARs, even in the presence of inhibitors and thus, may contribute to the sustained signaling that may lead to disease. We also discovered that peptidases such as trypsin IV can signal to neurons through PAR1 and PAR2 to induce pain and neurogenic inflammation and that certain proteases are upregulated during states of intestinal inflammation2,3 . We have also evaluated the contributions of peptidases and PARs to inflammation and pain transmission. In particular we have highlighted the molecular process by which PAR2 sensitize transient receptor potential channels (TRPs) to mediate nociception and neurogenic inflammation, through the release of neuropeptides4,5 .
Regulation of GPCR trafficking
Another of my research interests is to elucidate how peptidases and neuropeptides regulate the trafficking and signaling of GPCRs. For example, we showed that following activation, PAR2 is covalently modified by the addition of ubiquitin molecules to intracellular lysines residues. This modification directs the cellular machinery to traffic the receptor from the cell-surface, through the endosomal system to be degraded by peptidases in the lysosome, where signal transduction is irrevocably terminated6.
Recently my research has focused on proteolytic processes in endosomes. We discovered a new role for endothelin-converting enzyme-1. This endosomal peptidase, by degrading and altering agonist availability in endosomes, regulates the recycling of the neurokinin 1 receptor and calcitonin receptor-like receptor, the receptors for substance P (SP) and calcitonin gene-related peptide (CGRP), respectively. This mechanism resensitizes the pro-inflammatory effects of SP in vivo7,8 and promotes the resensitization of responses to CGRP in mesenteric arteries9. We also discovered that agonist availability in endosomes has profound effects on SP-induced mitogenic signaling from endosomes. We observed that endosomal proteolysis attenuates SP-induced mitogenic signaling in the nucleus to prevent cell death10. Thus, as endosomal proteolysis regulates the presence of GPCRs at the cell-surface (which is required for signaling) and the signaling of internalized GPCRs, targeting endosomal peptidases may represent a novel target for the treatment of peptide driven diseases.
Current Research
My current work is focused on understanding the role of the neuropeptides adrenomedullin (ADM) and CGRP in the trafficking and signaling of their receptors in the vascular and nervous systems. ADM and CGRP share multiple effects in the cardiovascular system, where they cause vasorelaxation and endothelial cell proliferation. In the nervous system both ADM and CGRP are important in the transmission of pain. ADM and CGRP and their receptors contribute to the pathophysiology of migraine, hypertension, ischemic heart disease, and cardiac and renal failure. Currently, CGRP receptor antagonists are in clinical trials for the treatment of migraine.
My work is also directed to understand the interplay between peptidases, PARs and TRPs in the development of inflammation and pain processes. We have previously shown that agonists of PAR2 sensitize TRPV1 and TRPV4 to contribute to inflammation and the sensation of pain. My laboratory aims to expand our knowledge of the basic molecular mechanisms that regulate peptidases, neuropeptides, GPCRs and TRPs. This is essential for understanding how vascular and nervous systems are regulated and will permit the development of novel therapies to treat human disease.
Selected publications
References
1. Cottrell, G. S., Amadesi, S., Grady, E. F. & Bunnett, N. W. Trypsin IV, a novel agonist of protease-activated receptors 2 and 4. J Biol Chem 279, 13532-13539, (2004).
2. Knecht, W., Cottrell, G. S., Amadesi, S., Mohlin, J., Skaregarde, A., Gedda, K., Peterson, A., Chapman, K., Hollenberg, M. D., Vergnolle, N. & Bunnett, N. W. Trypsin IV or mesotrypsin and p23 cleave protease-activated receptors 1 and 2 to induce inflammation and hyperalgesia. J Biol Chem 282, 26089-26100, (2007).
3. Cottrell, G. S., Amadesi, S., Pikios, S., Camerer, E., Willardsen, J. A., Murphy, B. R., Caughey, G. H., Wolters, P. J., Coughlin, S. R., Peterson, A., Knecht, W., Pothoulakis, C., Bunnett, N. W. & Grady, E. F. Protease-activated receptor 2, dipeptidyl peptidase I, and proteases mediate Clostridium difficile toxin A enteritis. Gastroenterology 132, 2422-2437, (2007).
4. Grant, A. D., Cottrell, G. S., Amadesi, S., Trevisani, M., Nicoletti, P., Materazzi, S., Altier, C., Cenac, N., Zamponi, G. W., Bautista-Cruz, F., Lopez, C. B., Joseph, E. K., Levine, J. D., Liedtke, W., Vanner, S., Vergnolle, N., Geppetti, P. & Bunnett, N. W. Protease-activated receptor 2 sensitizes the transient receptor potential vanilloid 4 ion channel to cause mechanical hyperalgesia in mice. J Physiol 578, 715-733, (2007).
5. Amadesi, S., Nie, J., Vergnolle, N., Cottrell, G. S., Grady, E. F., Trevisani, M., Manni, C., Geppetti, P., McRoberts, J. A., Ennes, H., Davis, J. B., Mayer, E. A. & Bunnett, N. W. Protease-activated receptor 2 sensitizes the capsaicin receptor transient receptor potential vanilloid receptor 1 to induce hyperalgesia. J Neurosci 24, 4300-4312, (2004).
6. Jacob, C., Cottrell, G. S., Gehringer, D., Schmidlin, F., Grady, E. F. & Bunnett, N. W. c-Cbl mediates ubiquitination, degradation, and down-regulation of human protease-activated receptor 2. J Biol Chem 280, 16076-16087, (2005).
7. Cattaruzza, F., Cottrell, G. S., Vaksman, N. & Bunnett, N. W. Endothelin-converting enzyme 1 promotes re-sensitization of neurokinin 1 receptor-dependent neurogenic inflammation. Br J Pharmacol 156, 730-739, (2009).
8. Roosterman, D., Cottrell, G. S., Padilla, B. E., Muller, L., Eckman, C. B., Bunnett, N. W. & Steinhoff, M. Endothelin-converting enzyme 1 degrades neuropeptides in endosomes to control receptor recycling. Proc Natl Acad Sci U S A 104, 11838-11843, (2007).
9. McNeish, A. J., Roux, B. T., Aylett, S-B., Van Den Brink, A. M. & Cottrell, G. S. Endosomal proteolysis regulates calcitonin gene-related peptide responses in mesenteric arteries. Br J Pharmacol 167, 1679-1690, (2012).
10. Cottrell, G. S., Padilla, B. E., Amadesi, S., Poole, D. P., Murphy, J. E., Hardt, M., Roosterman, D., Steinhoff, M. & Bunnett, N. W. Endosomal endothelin-converting enzyme-1: a regulator of beta-arrestin-dependent ERK signaling. J Biol Chem 284, 22411-22425, 2009).
Publications
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Roosterman, D.
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Cottrell, G.
ORCID: 0000-0001-9098-7627 (2023) Discovery of a second citric acid cycle complex. Heliyon , 9 (5). ISSN: 24058440 | doi: https://dx.doi.org/10.1016/j.heliyon.2023.e15968
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Asadpour, A.
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Yahaya, B.
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Bicknell, K.
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Cottrell, G.
ORCID: 0000-0001-9098-7627 , Widera, D.
ORCID: 0000-0003-1686-130X (2023) Uncovering the gray zone: mapping the global landscape of direct-to-consumer businesses offering interventions based on secretomes, extracellular vesicles, and exosomes. Stem cell research and therapy , 14 (1). ISSN: 1757-6512 | doi: https://dx.doi.org/10.1186/s13287-023-03335-2
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Bercea, C.
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Limbu, R.
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Behnam, K.
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Ng, K.
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Aziz, Q.
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Tinker, A.
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Tamagnini, F.
ORCID: 0000-0002-8741-5094 , Cottrell, G.
ORCID: 0000-0001-9098-7627 , McNeish, A. (2022) Omega-3 polyunsaturated fatty acid-induced vasodilation in mouse aorta and mesenteric arteries is not mediated by ATP-sensitive potassium channels. Frontiers in Physiology , 13 ISSN: 1664-042X | doi: https://dx.doi.org/10.3389/fphys.2022.1033216
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Kanapeckaitė, A.
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Mažeikienė, A.
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Geris, L.
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Burokienė, N.
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Cottrell, G.
ORCID: 0000-0001-9098-7627 , Widera, D.
ORCID: 0000-0003-1686-130X (2022) Computational pharmacology: new avenues for COVID-19 therapeutics search and better preparedness for future pandemic crises. Biophysical Chemistry , 290 ISSN: 0301-4622 | doi: https://dx.doi.org/10.1016/j.bpc.2022.106891
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Kanapeckaitė, A.
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Burokienė, N.
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Mažeikienė, A.
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Cottrell, G.
ORCID: 0000-0001-9098-7627 , Widera, D.
ORCID: 0000-0003-1686-130X (2021) Biophysics is reshaping our perception of the epigenome: from changing the landscape of how we study DNA-level epigenetic marks to enabling high-throughput applications. Biophysical Reports , 1 (2). ISSN: 2667-0747 | doi: https://dx.doi.org/10.1016/j.bpr.2021.100028
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Torre, E.
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Bicer, M.
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Cottrell, G.
ORCID: 0000-0001-9098-7627 , Widera, D.
ORCID: 0000-0003-1686-130X , Tamagnini, F.
ORCID: 0000-0002-8741-5094 (2021) Time-dependent reduction of calcium oscillations in adipose-derived stem cells differentiating towards adipogenic and osteogenic lineage. Biomolecules , 11 (10). ISSN: 2218-273X | doi: https://dx.doi.org/10.3390/biom11101400
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Roosterman, D.
and
Cottrell, G.
ORCID: 0000-0001-9098-7627 (2021) Rethinking the Citric Acid Cycle: connecting pyruvate carboxylase and citrate synthase to the flow of energy and material. International Journal of Molecular Sciences , 22 (2). pp 0. ISSN: 1422-0067 | doi: https://dx.doi.org/10.3390/ijms22020604
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Roosterman, D.
and
Cottrell, G.
ORCID: 0000-0001-9098-7627 (2021) The two-cell model of glucose metabolism: a hypothesis of schizophrenia. Molecular Psychiatry , 26 pp. 1738-1747. ISSN: 1476-5578 | doi: https://dx.doi.org/10.1038/s41380-020-00980-4
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Silveirinha, V.
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Lin, H.
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Tanifuji, S.
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Mochida, S.
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Cottrell, G.
ORCID: 0000-0001-9098-7627 , Cimarosti, H. , Stephens, G.
ORCID: 0000-0002-8966-4238 (2021) CaV2.2 (N-type) voltage-gated calcium channels are activated by SUMOylation pathways. Cell Calcium , 93 ISSN: 0143-4160 | doi: https://dx.doi.org/10.1016/j.ceca.2020.102326
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Bercea, C.
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Cottrell, G.
ORCID: 0000-0001-9098-7627 , Tamagnini, F.
ORCID: 0000-0002-8741-5094 , McNeish, A. (2021) Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) and hypertension: a review of vasodilatory mechanisms of DHA and EPA. British Journal of Pharmacology , 178 (4). pp. 860-877. ISSN: 0007-1188 | doi: https://dx.doi.org/10.1111/bph.15336
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Bicer, M.
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Cottrell, G.
ORCID: 0000-0001-9098-7627 , Widera, D.
ORCID: 0000-0003-1686-130X (2021) Impact of 3D cell culture on bone regeneration potential of mesenchymal stromal cells. Stem cell research and therapy , 12 ISSN: 1757-6512 | doi: https://dx.doi.org/10.1186/s13287-020-02094-8
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Bicer, M.
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Sheard, J.
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Iandolo, D.
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Boateng, S.
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Cottrell, G.
ORCID: 0000-0001-9098-7627 , Widera, D.
ORCID: 0000-0003-1686-130X (2020) Electrical stimulation of adipose-derived stem cells in 3D nanofibrillar cellulose increases their osteogenic potential. Biomolecules , 10 (12). ISSN: 2218-273X | doi: https://dx.doi.org/10.3390/biom10121696
- Crescente, M. , Armstrong, P. , Kirkby, N. , Edin, M. , Chan, M. , Lih, F. , Jiao, J. , Maffucci, T. , Allan, H. , Mein, C. , Gaston-Massuet, C. , Cottrell, G. , Mitchell, J. , Zeldin, D. , Herschman, H. , Warner, T. (2020) Profiling the eicosanoid networks that underlie the anti- and pro-thrombotic effects of aspirin. FASEB Journal , 34 (8). pp. 10027-10040. ISSN: 0892-6638 | doi: https://dx.doi.org/10.1096/fj.202000312R
- Roosterman, D. and Cottrell, G. (2020) Astrocytes and neurons communicate via a monocarboxylic acid shuttle. AIMS Neuroscience , 7 (2). pp. 94-106. ISSN: 2373-7972 | doi: https://dx.doi.org/10.3934/Neuroscience.2020007
- Stephens, G. and Cottrell, G. (2019) CACHD1: a new activity-modifying protein for voltage-gated calcium channels. Channels , 13 (1). pp. 120-123. ISSN: 1933-6969 | doi: https://dx.doi.org/10.1080/19336950.2019.1600968
- Widera, D. , Martinez-Aguilar, R. , Cottrell, G. (2019) Toll-like 4 and protease-activated receptor 2 in physiology and pathophysiology of the nervous system: more than just receptor cooperation?. Neural Regeneration Research , 14 (7). pp. 1196-1201. ISSN: 1876-7958 | doi: https://dx.doi.org/10.4103/1673-5374.251290
- Cottrell, G. (2018) CGRP receptor signalling pathways. Handbook of Experimental Pharmacology. Handbook of Experimental Pharmacology pp 0. | doi: https://dx.doi.org/10.1007/164_2018_130
- Cottrell, G. , Soubrane, C. , Hounshell, J. , Lin, H. , Owenson, V. , Rigby, M. , Cox, P. , Barker, B. , Ottolini, M. , Ince, S. , Bauer, C. , Perez-Reyes, E. , Patel, M. , Stevens, E. , Stephens, G. (2018) CACHD1 is an α2δ-like protein that modulates CaV3 voltage-gated calcium channel activity. The Journal of Neuroscience , 38 (4). pp. 9186-9201. ISSN: 1529-2401 | doi: https://dx.doi.org/10.1523/JNEUROSCI.3572-15.2018
- Roosterman, D. , Meyerhof, W. , Cottrell, G. (2018) Proton transport chains in glucose metabolism: mind the proton. Frontiers in Neuroscience , 12 ISSN: 1662-453X | doi: https://dx.doi.org/10.3389/fnins.2018.00404
- Limbu, R. , Cottrell, G. , McNeish, A. (2018) Characterisation of the vasodilation effects of DHA and EPA, n-3 PUFAs (fish oils), in rat aorta and mesenteric resistance arteries. PLoS ONE , 13 (2). ISSN: 1932-6203 | doi: https://dx.doi.org/10.1371/journal.pone.0192484
- Leksmono, C. , Manzoni, C. , Tomkins, J. , Lucchesi, W. , Cottrell, G. , Lewis, P. (2018) Measuring lactase enzymatic activity in the teaching lab. Journal of Visualized Experiments (138). ISSN: 1940-087X | doi: https://dx.doi.org/10.3791/54377
- Krüger, C. , Zeuner, M. , Cottrell, G. , Widera, D. , Heilemann, M. (2017) Quantitative single-molecule imaging of TLR4 reveals ligand-specific receptor dimerization. Science Signaling , 10 (503). ISSN: 1937-9145 | doi: https://dx.doi.org/10.1126/scisignal.aan1308
- Roux, B. , Bauer, C. , McNeish, A. , Ward, S. , Cottrell, G. (2017) The role of ubiquitination and hepatocyte growth factor-regulated tyrosine kinase substrate in the degradation of the adrenomedullin type I receptor. Scientific Reports , 7 (1). pp. 12389. ISSN: 2045-2322 | doi: https://dx.doi.org/10.1038/s41598-017-12585-z
- Zeuner, M. , Vallance, T. , Vaiyapuri, S. , Cottrell, G. , Widera, D. (2017) Development and characterisation of a novel NF-κB reporter cell line for investigation of neuroinflammation. Mediators of inflammation , 2017 ISSN: 0962-9351 | doi: https://dx.doi.org/10.1155/2017/6209865
- Zeuner, M. , Krueger, C. , Volk, K. , Bieback, K. , Cottrell, G. , Heilemann, M. , Widera, D. (2016) Biased signalling is an essential feature of TLR4 in glioma cells. Biochimica Et Biophysica Acta (BBA) - Molecular Cell Research , 1863 (12). pp. 3084-3095. ISSN: 0167-4889 | doi: https://dx.doi.org/10.1016/j.bbamcr.2016.09.016
- Roux, B. and Cottrell, G. (2014) G protein-coupled receptors: what a difference a 'partner' makes. International Journal of Molecular Sciences , 15 (1). pp. 1112-1142. ISSN: 1422-0067 | doi: https://dx.doi.org/10.3390/ijms15011112
- Jensen, D. , Godfrey, C. , Niklas, C. , Canals, M. , Kocan, M. , Poole, D. , Murphy, J. , Alemi, F. , Cottrell, G. , Korbmacher, C. , Lambert, N. , Bunnett, N. , Corvera, C. (2013) The bile acid receptor TGR5 does not interact with β-arrestins or traffic to endosomes but transmits sustained signals from plasma membrane rafts.. The Journal of biological chemistry , 288 (32). pp. 22942-22960. ISSN: 1083-351X | doi: https://dx.doi.org/10.1074/jbc.M113.455774
- Alemi, F. , Kwon, E. , Poole, D. , Lieu, T. , Lyo, V. , Cattaruzza, F. , Cevikbas, F. , Steinhoff, M. , Nassini, R. , Materazzi, S. , Guerrero-Alba, R. , Valdez-Morales, E. , Cottrell, G. , Schoonjans, K. , Geppetti, P. , Vanner, S. , Bunnett, N. , Corvera, C. (2013) The TGR5 receptor mediates bile acid-induced itch and analgesia. The Journal of Clinical Investigation , 123 (4). pp. 1513-1530. ISSN: 0021-9738 | doi: https://dx.doi.org/10.1172/JCI64551
- Cottrell, G. (2013) Roles of proteolysis in regulation of G protein-coupled receptor function. British Journal of Pharmacology , 168 (3). pp. 576-590. ISSN: 1476-5381 | doi: https://dx.doi.org/10.1111/j.1476-5381.2012.02234.x
- Cottrell, G. , Alemi, F. , Kirkland, J. , Grady, E. , Corvera, C. , Bhargava, A. (2012) Localization of calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1) in human gastrointestinal tract. Peptides , 35 (2). pp. 202-211. ISSN: 0196-9781 | doi: https://dx.doi.org/10.1016/j.peptides.2012.03.020
- McNeish, A. , Altayo-Jimenez, F. , Cottrell, G. , Garland, C. (2012) Statins and selective inhibition of Rho kinase protect small conductance calcium-activated potassium channel function (KCa2.3) in cerebral arteries. PLoS ONE , 7 (10). ISSN: 1932-6203 | doi: https://dx.doi.org/10.1371/journal.pone.0046735
- McNeish, A. , Roux, B. , Aylett, S. , Van Den Brink, A. , Cottrell, G. (2012) Endosomal proteolysis regulates calcitonin gene-related peptide responses in mesenteric arteries. British Journal of Pharmacology , 167 (8). pp. 1679-1690. ISSN: 1476-5381 | doi: https://dx.doi.org/10.1111/j.1476-5381.2012.02129.x
- Murphy, J. , Roosterman, D. , Cottrell, G. , Padilla, B. , Feld, M. , Brand, E. , Cedron, W. , Bunnett, N. , Steinhoff, M. (2011) Protein phosphatase 2A mediates resensitization of the neurokinin 1 receptor. American Journal of Physiology. Cell Physiology , 301 (4). pp. C780-C791. ISSN: 1522-1563 | doi: https://dx.doi.org/10.1152/ajpcell.00096.2011
- Pelayo, J. , Poole, D. , Steinhoff, M. , Cottrell, G. , Bunnett, N. (2011) Endothelin-converting enzyme-1 regulates trafficking and signalling of the neurokinin 1 receptor in endosomes of myenteric neurones. Journal of Physiology , 589 (21). pp. 5213-5230. ISSN: 1469-7793 | doi: https://dx.doi.org/10.1113/jphysiol.2011.214452
- Bunnett, N. and Cottrell, G. (2010) Trafficking and signaling of G protein-coupled receptors in the nervous system: implications for disease and therapy. CNS & Neurological Disorders - Drug Targets , 9 (5). pp. 539-556. ISSN: 1996-3181 | doi: https://dx.doi.org/10.2174/187152710793361621
- Eilers, H. , Cattaruzza, F. , Nassini, R. , Materazzi, S. , Andre, E. , Chu, C. , Cottrell, G. , Schumacher, M. , Geppetti, P. , Bunnett, N. (2010) Pungent general anesthetics activate transient receptor potential-A1 to produce hyperalgesia and neurogenic bronchoconstriction. Anesthesiology , 112 (6). pp. 1452-1463. ISSN: 1528-1175 | doi: https://dx.doi.org/10.1097/ALN.0b013e3181d94e00
- Poole, D. , Godfrey, C. , Cattaruzza, F. , Cottrell, G. , Kirkland, J. , Pelayo, J. , Bunnett, N. , Corvera, C. (2010) Expression and function of the bile acid receptor GpBAR1 (TGR5) in the murine enteric nervous system. Neurogastroenterology and Motility , 22 (7). pp. 814-e228. ISSN: 1365-2982 | doi: https://dx.doi.org/10.1111/j.1365-2982.2010.01487.x
- Amadesi, S. , Grant, A. , Cottrell, G. , Vaksmam, N. , Poole, D. , Rozengurt, E. , Bunnett, N. (2009) Protein kinase D isoforms are expressed in rat and mouse primary sensory neurons and are activated by agonists of protease-activated receptor 2. Journal of Comparative Neurology , 516 (2). pp. 141-156. ISSN: 1096-9861 | doi: https://dx.doi.org/10.1002/cne.22104
- Cattaruzza, F. , Cottrell, G. , Vaksman, N. , Bunnett, N. (2009) Endothelin-converting enzyme 1 promotes re-sensitization of neurokinin 1 receptor-dependent neurogenic inflammation. British Journal of Pharmacology , 156 (5). pp. 730-739. ISSN: 1476-5381 | doi: https://dx.doi.org/10.1111/j.1476-5381.2008.00039.x
- Cottrell, G. , Padilla, B. , Amadesi, S. , Poole, D. , Murphy, J. , Hardt, M. , Roosterman, D. , Steinhoff, M. , Bunnett, N. (2009) Endosomal endothelin-converting enzyme-1: a regulator of beta-arrestin-dependent ERK signaling. Journal of Biological Chemistry , 284 (33). pp. 22411-22425. ISSN: 1083-351X | doi: https://dx.doi.org/10.1074/jbc.M109.026674
- Hasdemir, B. , Murphy, J. , Cottrell, G. , Bunnett, N. (2009) Endosomal deubiquitinating enzymes control ubiquitination and down-regulation of protease-activated receptor 2. Journal of Biological Chemistry , 284 (41). pp. 28453-28466. ISSN: 1083-351X | doi: https://dx.doi.org/10.1074/jbc.M109.025692
- Murphy, J. , Padilla, B. , Hasdemir, B. , Cottrell, G. , Bunnett, N. (2009) Endosomes: a legitimate platform for the signaling train. Proceedings of the National Academy of Sciences of the United States of America , 106 (42). pp. 17615-17622. ISSN: 1091-6490 | doi: https://dx.doi.org/10.1073/pnas.0906541106
- Roosterman, D. , Kempkes, C. , Cottrell, G. , Padilla, B. , Bunnett, N. , Turck, C. , Steinhoff, M. (2008) Endothelin-converting enzyme-1 degrades internalized somatostatin-14. Endocrinology , 149 (5). pp. 2200-2207. ISSN: 1945-7170 | doi: https://dx.doi.org/10.1210/en.2007-1628
- Cenac, N. , Andrews, C. , Holzhausen, M. , Chapman, K. , Cottrell, G. , Andrade-Gordon, P. , Steinhoff, M. , Barbara, G. , Beck, P. , Bunnett, N. , Sharkey, K. , Ferraz, J. , Shaffer, E. , Vergnolle, N. (2007) Role for protease activity in visceral pain in irritable bowel syndrome. The Journal of Clinical Investigation , 117 (3). pp. 636-647. ISSN: 0021-9738 | doi: https://dx.doi.org/10.1172/JCI29255
- Cottrell, G. , Amadesi, S. , Pikios, S. , Camerer, E. , Willardsen, J. , Murphy, B. , Caughey, G. , Wolters, P. , Coughlin, S. , Peterson, A. , Knecht, W. , Pothoulakis, C. , Bunnett, N. , Grady, E. (2007) Protease-activated receptor 2, dipeptidyl peptidase I, and proteases mediate Clostridium difficile toxin A enteritis. Gastroenterology , 132 (7). pp. 2422-2437. ISSN: 0016-5085 | doi: https://dx.doi.org/10.1053/j.gastro.2007.03.101
- Cottrell, G. , Padilla, B. , Pikios, S. , Roosterman, D. , Steinhoff, M. , Grady, E. , Bunnett, N. (2007) Post-endocytic sorting of calcitonin receptor-like receptor and receptor activity-modifying protein 1. The Journal of Biological Chemistry , 282 (16). pp. 12260-12271. ISSN: 1083-351X | doi: https://dx.doi.org/10.1074/jbc.M606338200
- Gazzieri, D. , Trevisani, M. , Springer, J. , Harrison, S. , Cottrell, G. , Andre, E. , Nicoletti, P. , Massi, D. , Zecchi, S. , Nosi, D. , Santucci, M. , Gerard, N. , Lucattelli, M. , Lungarella, G. , Fischer, A. , Grady, E. , Bunnett, N. , Geppetti, P. (2007) Substance P released by TRPV1-expressing neurons produces reactive oxygen species that mediate ethanol-induced gastric injury. Free Radical Biology and Medicine , 43 (4). pp. 581-589. ISSN: 0891-5849 | doi: https://dx.doi.org/10.1016/j.freeradbiomed.2007.05.018
- Grant, A. , Cottrell, G. , Amadesi, S. , Trevisani, M. , Nicoletti, P. , Materazzi, S. , Altier, C. , Cenac, N. , Zamponi, G. , Bautista-Cruz, F. , Lopez, C. , Joseph, E. , Levine, J. , Liedtke, W. , Vanner, S. , Vergnolle, N. , Geppetti, P. , Bunnett, N. (2007) Protease-activated receptor 2 sensitizes the transient receptor potential vanilloid 4 ion channel to cause mechanical hyperalgesia in mice. Journal of Physiology , 578 (3). pp. 715-733. ISSN: 0022-3751 | doi: https://dx.doi.org/10.1113/jphysiol.2006.121111
- Hasdemir, B. , Bunnett, N. , Cottrell, G. (2007) Hepatocyte growth factor-regulated tyrosine kinase substrate (HRS) mediates post-endocytic trafficking of protease-activated receptor 2 and calcitonin receptor-like receptor. The Journal of Biological Chemistry , 282 (40). pp. 29646-57. ISSN: 1083-351X | doi: https://dx.doi.org/10.1074/jbc.M702974200
- Kirkland, J. , Cottrell, G. , Bunnett, N. , Corvera, C. (2007) Agonists of protease-activated receptors 1 and 2 stimulate electrolyte secretion from mouse gallbladder. American Journal of Physiology Gastrointestinal and Liver Physiology , 293 (1). pp. G335-G346. ISSN: 0193-1857 | doi: https://dx.doi.org/10.1152/ajpgi.00425.2006
- Knecht, W. , Cottrell, G. , Amadesi, S. , Mohlin, J. , Skaregarde, A. , Gedda, K. , Peterson, A. , Chapman, K. , Hollenberg, M. , Vergnolle, N. , Bunnett, N. (2007) Trypsin IV or mesotrypsin and p23 cleave protease-activated receptors 1 and 2 to induce inflammation and hyperalgesia. The Journal of Biological Chemistry , 282 (36). pp. 26089-26100. ISSN: 1083-351X | doi: https://dx.doi.org/10.1074/jbc.M703840200
- Padilla, B. , Cottrell, G. , Roosterman, D. , Pikios, S. , Muller, L. , Steinhoff, M. , Bunnett, N. (2007) Endothelin-converting enzyme-1 regulates endosomal sorting of calcitonin receptor-like receptor and beta-arrestins. Journal of Cell Biology , 179 (5). pp. 981-997. ISSN: 0021-9525 | doi: https://dx.doi.org/10.1083/jcb.200704053
- Roosterman, D. , Cottrell, G. , Padilla, B. , Muller, L. , Eckman, C. , Bunnett, N. , Steinhoff, M. (2007) Endothelin-converting enzyme 1 degrades neuropeptides in endosomes to control receptor recycling. Proceedings of the National Academy of Sciences of the United States of America , 104 (28). pp. 11838-11843. ISSN: 0027-8424 | doi: https://dx.doi.org/10.1073/pnas.0701910104
- Roosterman, D. , Kreuzer, O. , Brune, N. , Cottrell, G. , Bunnett, N. , Meyerhof, W. , Steinhoff, M. (2007) Agonist-induced endocytosis of rat somatostatin receptor 1. Endocrinology , 148 (3). pp. 1050-1058. ISSN: 1945-7170 | doi: https://dx.doi.org/10.1210/en.2006-1600
- Trevisani, M. , Siemens, J. , Materazzi, S. , Bautista, D. , Nassini, R. , Campi, B. , Imamachi, N. , Andre, E. , Patacchini, R. , Cottrell, G. , Gatti, R. , Basbaum, A. , Bunnett, N. , Julius, D. , Geppetti, P. (2007) 4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1. Proceedings of the National Academy of Sciences of the United States of America , 104 (33). pp. 13519-13524. ISSN: 0027-8424 | doi: https://dx.doi.org/10.1073/pnas.0705923104
- Amadesi, S. , Cottrell, G. , Divino, L. , Chapman, K. , Grady, E. , Bautista, F. , Karanjia, R. , Barajas-Lopez, C. , Vanner, S. , Vergnolle, N. , Bunnett, N. (2006) Protease-activated receptor 2 sensitizes TRPV1 by protein kinase Cepsilon- and A-dependent mechanisms in rats and mice. Journal of Physiology , 575 (2). pp. 555-571. ISSN: 0022-3751 | doi: https://dx.doi.org/10.1113/jphysiol.2006.111534
- Cottrell, G. , Padilla, B. , Pikios, S. , Roosterman, D. , Steinhoff, M. , Gehringer, D. , Grady, E. , Bunnett, N. (2006) Ubiquitin-dependent down-regulation of the neurokinin-1 receptor. The Journal of Biological Chemistry , 281 (38). pp. 27773-27783. ISSN: 1083-351X | doi: https://dx.doi.org/10.1074/jbc.M603369200
- Oikonomopoulou, K. , Hansen, K. , Saifeddine, M. , Tea, I. , Blaber, M. , Blaber, S. , Scarisbrick, I. , Andrade-Gordon, P. , Cottrell, G. , Bunnett, N. , Diamandis, E. , Hollenberg, M. (2006) Proteinase-activated receptors, targets for kallikrein signaling. The Journal of Biological Chemistry , 281 (43). pp. 32095-32112. ISSN: 1083-351X | doi: https://dx.doi.org/10.1074/jbc.M513138200
- Cottrell, G. , Roosterman, D. , Marvizon, J. , Song, B. , Wick, E. , Pikios, S. , Wong, H. , Berthelier, C. , Tang, Y. , Sternini, C. , Bunnett, N. , Grady, E. (2005) Localization of calcitonin receptor-like receptor and receptor activity modifying protein 1 in enteric neurons, dorsal root ganglia, and the spinal cord of the rat. Journal of Comparative Neurology , 490 (3). pp. 239-255. ISSN: 1096-9861 | doi: https://dx.doi.org/10.1002/cne.20669
- Dulon, S. , Leduc, D. , Cottrell, G. , D'Alayer, J. , Hansen, K. , Bunnett, N. , Hollenberg, M. , Pidard, D. , Chignard, M. (2005) Pseudomonas aeruginosa elastase disables proteinase-activated receptor 2 in respiratory epithelial cells. American Journal of Respiratory Cell and Molecular Biology , 32 (5). pp. 411-419. ISSN: 1044-1549 | doi: https://dx.doi.org/10.1165/rcmb.2004-0274OC
- Jacob, C. , Cottrell, G. , Gehringer, D. , Schmidlin, F. , Grady, E. , Bunnett, N. (2005) c-Cbl mediates ubiquitination, degradation, and down-regulation of human protease-activated receptor 2. The Journal of Biological Chemistry , 280 (16). pp. 76-87. ISSN: 1083-351X | doi: https://dx.doi.org/10.1074/jbc.M500109200
- Jacob, C. , Yang, P. , Darmoul, D. , Amadesi, S. , Saito, T. , Cottrell, G. , Coelho, A. , Singh, P. , Grady, E. , Perdue, M. , Bunnett, N. (2005) Mast cell tryptase controls paracellular permeability of the intestine: role of protease-activated receptor 2 and beta-arrestins. Journal of Biological Chemistry , 280 (31). pp. 936-948. ISSN: 1083-351X | doi: https://dx.doi.org/10.1074/jbc.M506338200
- Amadesi, S. , Nie, J. , Vergnolle, N. , Cottrell, G. , Grady, E. , Trevisani, M. , Manni, C. , Geppetti, P. , McRoberts, J. , Ennes, H. , Davis, J. , Mayer, E. , Bunnett, N. (2004) Protease-activated receptor 2 sensitizes the capsaicin receptor transient receptor potential vanilloid receptor 1 to induce hyperalgesia. The Journal of Neuroscience , 24 (18). pp. 4300-4312. ISSN: 1529-2401 | doi: https://dx.doi.org/10.1523/JNEUROSCI.5679-03.2004
- Barbara, G. , Stanghellini, V. , De Giorgio, R. , Cremon, C. , Cottrell, G. , Santini, D. , Pasquinelli, G. , Morselli-Labate, A. , Grady, E. , Bunnett, N. , Collins, S. , Corinaldesi, R. (2004) Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. Gastroenterology , 126 (3). pp. 693-702. ISSN: 0016-5085 | doi: https://dx.doi.org/10.1053/j.gastro.2003.11.055
- Cottrell, G. , Amadesi, S. , Grady, E. , Bunnett, N. (2004) Trypsin IV, a novel agonist of protease-activated receptors 2 and 4. Journal of Biological Chemistry , 279 (14). pp. 13532-13539. ISSN: 1083-351X | doi: https://dx.doi.org/10.1074/jbc.M312090200
- Roosterman, D. , Cottrell, G. , Schmidlin, F. , Steinhoff, M. , Bunnett, N. (2004) Recycling and resensitization of the neurokinin 1 receptor: influence of agonist concentration and Rab GTPases. The Journal of Biological Chemistry , 279 (29). pp. 30670-30679. ISSN: 1083-351X | doi: https://dx.doi.org/10.1074/jbc.M402479200
- Cottrell, G. , Amadesi, S. , Schmidlin, F. , Bunnett, N. (2003) Protease-activated receptor 2: activation, signalling and function. Biochemical Society Transactions , 31 (6). pp. 1191-1197. ISSN: 1470-8752
- Reed, D. , Barajas-Lopez, C. , Cottrell, G. , Velazquez-Rocha, S. , Dery, O. , Grady, E. , Bunnett, N. , Vanner, S. (2003) Mast cell tryptase and proteinase-activated receptor 2 induce hyperexcitability of guinea-pig submucosal neurons. Journal of Physiology , 547 (2). pp. 531-542. ISSN: 0022-3751 | doi: https://dx.doi.org/10.1113/jphysiol.2002.032011
- Cottrell, G. , Coelho, A. , Bunnett, N. (2002) Protease-activated receptors: the role of cell-surface proteolysis in signalling. Essays in Biochemistry , 38 pp. 169-183. ISSN: 0071-1365
- Cottrell, G. , Hooper, N. , Turner, A. (2000) Cloning, expression, and characterization of human cytosolic aminopeptidase P: a single manganese(II)-dependent enzyme. Biochemistry , 39 (49). pp. 15121-15128. ISSN: 0006-2960 | doi: https://dx.doi.org/10.1021/bi001585c
- Cottrell, G. , Hyde, R. , Lim, J. , Parsons, M. , Hooper, N. , Turner, A. (2000) Identification of critical residues in the active site of porcine membrane-bound aminopeptidase P. Biochemistry , 39 (49). pp. 15129-15135. ISSN: 0006-2960 | doi: https://dx.doi.org/10.1021/bi0015865
- Cottrell, G. , Hyde, . , Hooper, . , Turner, . (1998) The cloning and functional expression of human pancreatic aminopeptidase P. Biochemical Society Transactions , 26 (3). pp. S248. ISSN: 1470-8752