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1. THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Overview

Author

Alexander, Stephen PH, Kelly, Eamonn, Marrion, Neil V, Peters, John A, Faccenda, Elena, Harding, Simon D, Pawson, Adam J, Sharman, Joanna L, Southan, Christopher, Buneman, O Peter, Cidlowski, John A, Christopoulos, Arthur, Davenport, Anthony P, Fabbro, Doriano, Spedding, Michael, Striessnig, Jörg, Davies, Jamie A, Collaborators, CGTP, Abbracchio, M‐P, Aldrich, R, Al‐Hosaini, K, Arumugam, TV, Attali, B, Bäck, M, Barnes, NM, Bathgate, R, Beart, PM, Becirovic, E, Bettler, B, Biel, M, Birdsall, NJ, Blaho, V, Boison, D, Bräuner‐osborne, H, Bröer, S, Bryant, C, Burnstock, G, Calo, G, Catterall, WA, Ceruti, S, Chan, SL, Chandy, KG, Chazot, P, Chiang, N, Chun, JJ, Chung, J‐J, Clapham, DE, Clapp, L, Connor, MA, Cox, HM, Davies, P, Dawson, PA, Decaen, P, Dent, G, Doherty, P, Douglas, SD, Dubocovich, ML, Fong, TM, Fowler, CJ, Frantz, A, Fuller, P, Fumagalli, M, Futerman, AH, Gainetdinov, RR, Gershengorn, MA, Goldin, A, Goldstein, SAN, Goudet, C, Gregory, K, Grissmer, S, Gundlach, AL, Hagenbuch, B, Hamann, J, Hammond, Hancox, JC, Hanson, J, Hanukoglu, I, Hay, DL, Hobbs, AJ, Hollenberg, AN, Holliday, ND, Hoyer, D, Ijzerman, AP, Inui, KI, Irving, AJ, Ishii, S, Jacobson, KA, Jan, LY, Jarvis, MF, Jensen, R, Jockers, R, Kaczmarek, LK, Kanai, Y, Karnik, S, Kellenberger, S, Kemp, S, Kennedy, C, Kerr, ID, Kihara, Y, and Kukkonen, J

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Generic health relevance, Databases, Pharmaceutical, Humans, Knowledge Bases, Ligands, Proteins, CGTP Collaborators, Pharmacology & Pharmacy, Pharmacology and pharmaceutical sciences
Abstract

The Concise Guide to PHARMACOLOGY 2017/18 is the third in this series of biennial publications. This version provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13882/full. In addition to this overview, in which are identified 'Other protein targets' which fall outside of the subsequent categorisation, there are eight areas of focus: G protein-coupled receptors, ligand-gated ion channels, voltage-gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2017, and supersedes data presented in the 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature Committee of the Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.

Published
2017

2. The Concise Guide to PHARMACOLOGY 2015/16: Overview

Author

Alexander, Stephen PH, Kelly, Eamonn, Marrion, Neil, Peters, John A, Benson, Helen E, Faccenda, Elena, Pawson, Adam J, Sharman, Joanna L, Southan, Christopher, Buneman, O Peter, Catterall, William A, Cidlowski, John A, Davenport, Anthony P, Fabbro, Doriano, Fan, Grace, McGrath, John C, Spedding, Michael, Davies, Jamie A, Collaborators, CGTP, Aldrich, R, Attali, B, Bäck, Ml, Barnes, NM, Bathgate, R, Beart, PM, Becirovic, E, Biel, M, Birdsall, NJ, Boison, D, Bräuner‐Osborne, H, Bröer, S, Bryant, C, Burnstock, G, Burris, T, Cain, D, Calo, G, Chan, SL, Chandy, KG, Chiang, N, Christakos, S, Christopoulos, A, Chun, JJ, Chung, J‐J, Clapham, DE, Connor, MA, Coons, L, Cox, HM, Dautzenberg, FM, Dent, G, Douglas, SD, Dubocovich, ML, Edwards, DP, Farndale, R, Fong, TM, Forrest, D, Fowler, CJ, Fuller, P, Gainetdinov, RR, Gershengorn, MA, Goldin, A, Goldstein, SAN, Grimm, SL, Grissmer, S, Gundlach, AL, Hagenbuch, B, Hammond, Hancox, JC, Hartig, S, Hauger, RL, Hay, DL, Hébert, T, Hollenberg, AN, Holliday, ND, Hoyer, D, Ijzerman, AP, Inui, KI, Ishii, S, Jacobson, KA, Jan, LY, Jarvis, GE, Jensen, R, Jetten, A, Jockers, R, Kaczmarek, LK, Kanai, Y, Kang, HS, Karnik, S, Kerr, ID, Korach, KS, Lange, CA, Larhammar, D, Leeb‐Lundberg, F, Leurs, R, Lolait, SJ, Macewan, D, Maguire, JJ, May, JM, Mazella, J, Mcardle, CA, and Mcdonnell, DP

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, 1.1 Normal biological development and functioning, Generic health relevance, Animals, Databases, Pharmaceutical, Humans, Pharmacology, CGTP Collaborators, Pharmacology & Pharmacy, Pharmacology and pharmaceutical sciences
Abstract

The Concise Guide to PHARMACOLOGY 2015/16 provides concise overviews of the key properties of over 1750 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. The full contents can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13347/full. This compilation of the major pharmacological targets is divided into eight areas of focus: G protein-coupled receptors, ligand-gated ion channels, voltage-gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The Concise Guide is published in landscape format in order to facilitate comparison of related targets. It is a condensed version of material contemporary to late 2015, which is presented in greater detail and constantly updated on the website www.guidetopharmacology.org, superseding data presented in the previous Guides to Receptors & Channels and the Concise Guide to PHARMACOLOGY 2013/14. It is produced in conjunction with NC-IUPHAR and provides the official IUPHAR classification and nomenclature for human drug targets, where appropriate. It consolidates information previously curated and displayed separately in IUPHAR-DB and GRAC and provides a permanent, citable, point-in-time record that will survive database updates.

Published
2015

4. The Concise Guide to PHARMACOLOGY 2023/24: G protein-coupled receptors

Author

Alexander, SPH, Christopoulos, A, Davenport, AP, Kelly, E, Mathie, AA, Peters, JA, Veale, EL, Armstrong, JF, Faccenda, E, Harding, SD, Davies, JA, Abbracchio, MP, Abraham, G, Agoulnik, A, Alexander, W, Al-hosaini, K, Back, M, Baker, JG, Barnes, NM, Bathgate, R, Beaulieu, J-M, Beck-Sickinger, AG, Behrens, M, Bernstein, KE, Bettler, B, Birdsall, NJM, Blaho, V, Boulay, F, Bousquet, C, Brauner-Osborne, H, Burnstock, G, Calo, G, Castano, JP, Catt, KJ, Ceruti, S, Chazot, P, Chiang, N, Chini, B, Chun, J, Cianciulli, A, Civelli, O, Clapp, LH, Couture, R, Cox, HM, Csaba, Z, Dahlgren, C, Dent, G, Douglas, SD, Dournaud, P, Eguchi, S, Escher, E, Filardo, EJ, Fong, T, Fumagalli, M, Gainetdinov, RR, Garelja, ML, de Gasparo, M, Gerard, C, Gershengorn, M, Gobeil, F, Goodfriend, TL, Goudet, C, Gratz, L, Gregory, KJ, Gundlach, AL, Hamann, J, Hanson, J, Hauger, RL, Hay, DL, Heinemann, A, Herr, D, Hollenberg, MD, Holliday, ND, Horiuchi, M, Hoyer, D, Hunyady, L, Husain, A, Ijzerman, AP, Inagami, T, Jacobson, KA, Jensen, RT, Jockers, R, Jonnalagadda, D, Karnik, S, Kaupmann, K, Kemp, J, Kennedy, C, Kihara, Y, Kitazawa, T, Kozielewicz, P, Kreienkamp, H-J, Kukkonen, JP, Langenhan, T, Larhammar, D, Leach, K, Lecca, D, Lee, JD, Leeman, SE, Leprince, J, Li, XX, Lolait, SJ, Lupp, A, Macrae, R, Maguire, J, Malfacini, D, Mazella, J, McArdle, CA, Melmed, S, Michel, MC, Miller, LJ, Mitolo, V, Mouillac, B, Mueller, CE, Murphy, PM, Nahon, J-L, Ngo, T, Norel, X, Nyimanu, D, O'Carroll, A-M, Offermanns, S, Panaro, MA, Parmentier, M, Pertwee, RG, Pin, J-P, Prossnitz, ER, Quinn, M, Ramachandran, R, Ray, M, Reinscheid, RK, Rondard, P, Rovati, GE, Ruzza, C, Sanger, GJ, Schoeneberg, T, Schulte, G, Schulz, S, Segaloff, DL, Serhan, CN, Singh, KD, Smith, CM, Stoddart, LA, Sugimoto, Y, Summers, R, Tan, VP, Thal, D, Thomas, WW, Timmermans, PBMWM, Tirupula, K, Toll, L, Tulipano, G, Unal, H, Unger, T, Valant, C, Vanderheyden, P, Vaudry, D, Vaudry, H, Vilardaga, J-P, Walker, CS, Wang, JM, Ward, DT, Wester, H-J, Willars, GB, Williams, TL, Woodruff, TM, Yao, C, Ye, RD, Alexander, SPH, Christopoulos, A, Davenport, AP, Kelly, E, Mathie, AA, Peters, JA, Veale, EL, Armstrong, JF, Faccenda, E, Harding, SD, Davies, JA, Abbracchio, MP, Abraham, G, Agoulnik, A, Alexander, W, Al-hosaini, K, Back, M, Baker, JG, Barnes, NM, Bathgate, R, Beaulieu, J-M, Beck-Sickinger, AG, Behrens, M, Bernstein, KE, Bettler, B, Birdsall, NJM, Blaho, V, Boulay, F, Bousquet, C, Brauner-Osborne, H, Burnstock, G, Calo, G, Castano, JP, Catt, KJ, Ceruti, S, Chazot, P, Chiang, N, Chini, B, Chun, J, Cianciulli, A, Civelli, O, Clapp, LH, Couture, R, Cox, HM, Csaba, Z, Dahlgren, C, Dent, G, Douglas, SD, Dournaud, P, Eguchi, S, Escher, E, Filardo, EJ, Fong, T, Fumagalli, M, Gainetdinov, RR, Garelja, ML, de Gasparo, M, Gerard, C, Gershengorn, M, Gobeil, F, Goodfriend, TL, Goudet, C, Gratz, L, Gregory, KJ, Gundlach, AL, Hamann, J, Hanson, J, Hauger, RL, Hay, DL, Heinemann, A, Herr, D, Hollenberg, MD, Holliday, ND, Horiuchi, M, Hoyer, D, Hunyady, L, Husain, A, Ijzerman, AP, Inagami, T, Jacobson, KA, Jensen, RT, Jockers, R, Jonnalagadda, D, Karnik, S, Kaupmann, K, Kemp, J, Kennedy, C, Kihara, Y, Kitazawa, T, Kozielewicz, P, Kreienkamp, H-J, Kukkonen, JP, Langenhan, T, Larhammar, D, Leach, K, Lecca, D, Lee, JD, Leeman, SE, Leprince, J, Li, XX, Lolait, SJ, Lupp, A, Macrae, R, Maguire, J, Malfacini, D, Mazella, J, McArdle, CA, Melmed, S, Michel, MC, Miller, LJ, Mitolo, V, Mouillac, B, Mueller, CE, Murphy, PM, Nahon, J-L, Ngo, T, Norel, X, Nyimanu, D, O'Carroll, A-M, Offermanns, S, Panaro, MA, Parmentier, M, Pertwee, RG, Pin, J-P, Prossnitz, ER, Quinn, M, Ramachandran, R, Ray, M, Reinscheid, RK, Rondard, P, Rovati, GE, Ruzza, C, Sanger, GJ, Schoeneberg, T, Schulte, G, Schulz, S, Segaloff, DL, Serhan, CN, Singh, KD, Smith, CM, Stoddart, LA, Sugimoto, Y, Summers, R, Tan, VP, Thal, D, Thomas, WW, Timmermans, PBMWM, Tirupula, K, Toll, L, Tulipano, G, Unal, H, Unger, T, Valant, C, Vanderheyden, P, Vaudry, D, Vaudry, H, Vilardaga, J-P, Walker, CS, Wang, JM, Ward, DT, Wester, H-J, Willars, GB, Williams, TL, Woodruff, TM, Yao, C, and Ye, RD

Abstract

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.16177. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.

Published
2023

9. Purinergic Signalling in Gut

Author

Burnstock, G., Born, G. V. R., editor, Ganten, D., editor, Herken, H., editor, Starke, K., editor, Taylor, P., editor, Abbracchio, Maria Pia, editor, and Williams, Michael, editor

Published
2001
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18. THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: G protein-coupled receptors

Author

Alexander, SPH, Christopoulos, A, Davenport, AP, Kelly, E, Mathie, A, Peters, JA, Veale, EL, Armstrong, JF, Faccenda, E, Harding, SD, Pawson, AJ, Southan, C, Davies, JA, Abbracchio, MP, Alexander, W, Al-hosaini, K, Baeck, M, Barnes, NM, Bathgate, R, Beaulieu, J-M, Bernstein, KE, Bettler, B, Birdsall, NJM, Blaho, V, Boulay, F, Bousquet, C, Braeuner-Osborne, H, Burnstock, G, Calo, G, Castano, JP, Catt, K, Ceruti, S, Chazot, P, Chiang, N, Chini, B, Chun, J, Cianciulli, A, Civelli, O, Clapp, LH, Couture, R, Csaba, Z, Dahlgren, C, Dent, G, Singh, KD, Douglas, SD, Dournaud, P, Eguchi, S, Escher, E, Filardo, EJ, Fong, T, Fumagalli, M, Gainetdinov, RR, de Gasparo, M, Gerard, C, Gershengorn, M, Gobeil, F, Goodfriend, TL, Goudet, C, Gregory, KJ, Gundlach, AL, Hamann, J, Hanson, J, Hauger, RL, Hay, DL, Heinemann, A, Hollenberg, MD, Holliday, ND, Horiuchi, M, Hoyer, D, Hunyady, L, Husain, A, IJzerman, AP, Inagami, T, Jacobson, KA, Jensen, RT, Jockers, R, Jonnalagadda, D, Karnik, S, Kaupmann, K, Kemp, J, Kennedy, C, Kihara, Y, Kitazawa, T, Kozielewicz, P, Kreienkamp, H-J, Kukkonen, JP, Langenhan, T, Leach, K, Lecca, D, Lee, JD, Leeman, SE, Leprince, J, Li, XX, Williams, TL, Lolait, SJ, Lupp, A, Macrae, R, Maguire, J, Mazella, J, McArdle, CA, Melmed, S, Michel, MC, Miller, LJ, Mitolo, V, Mouillac, B, Mueller, CE, Murphy, P, Nahon, J-L, Ngo, T, Norel, X, Nyimanu, D, Ocarroll, A-M, Offermanns, S, Panaro, MA, Parmentier, M, Pertwee, RG, Pin, J-P, Prossnitz, ER, Quinn, M, Ramachandran, R, Ray, M, Reinscheid, RK, Rondard, P, Rovati, GE, Ruzza, C, Sanger, GJ, Schoeneberg, T, Schulte, G, Schulz, S, Segaloff, DL, Serhan, CN, Stoddart, LA, Sugimoto, Y, Summers, R, Tan, VP, Thal, D, Thomas, WW, Timmermans, PMWM, Tirupula, K, Tulipano, G, Unal, H, Unger, T, Valant, C, Vanderheyden, P, Vaudry, D, Vaudry, H, Vilardaga, J-P, Walker, CS, Wang, JM, Ward, DT, Wester, H-J, Willars, GB, Woodruff, TM, Yao, C, Ye, RD, Alexander, SPH, Christopoulos, A, Davenport, AP, Kelly, E, Mathie, A, Peters, JA, Veale, EL, Armstrong, JF, Faccenda, E, Harding, SD, Pawson, AJ, Southan, C, Davies, JA, Abbracchio, MP, Alexander, W, Al-hosaini, K, Baeck, M, Barnes, NM, Bathgate, R, Beaulieu, J-M, Bernstein, KE, Bettler, B, Birdsall, NJM, Blaho, V, Boulay, F, Bousquet, C, Braeuner-Osborne, H, Burnstock, G, Calo, G, Castano, JP, Catt, K, Ceruti, S, Chazot, P, Chiang, N, Chini, B, Chun, J, Cianciulli, A, Civelli, O, Clapp, LH, Couture, R, Csaba, Z, Dahlgren, C, Dent, G, Singh, KD, Douglas, SD, Dournaud, P, Eguchi, S, Escher, E, Filardo, EJ, Fong, T, Fumagalli, M, Gainetdinov, RR, de Gasparo, M, Gerard, C, Gershengorn, M, Gobeil, F, Goodfriend, TL, Goudet, C, Gregory, KJ, Gundlach, AL, Hamann, J, Hanson, J, Hauger, RL, Hay, DL, Heinemann, A, Hollenberg, MD, Holliday, ND, Horiuchi, M, Hoyer, D, Hunyady, L, Husain, A, IJzerman, AP, Inagami, T, Jacobson, KA, Jensen, RT, Jockers, R, Jonnalagadda, D, Karnik, S, Kaupmann, K, Kemp, J, Kennedy, C, Kihara, Y, Kitazawa, T, Kozielewicz, P, Kreienkamp, H-J, Kukkonen, JP, Langenhan, T, Leach, K, Lecca, D, Lee, JD, Leeman, SE, Leprince, J, Li, XX, Williams, TL, Lolait, SJ, Lupp, A, Macrae, R, Maguire, J, Mazella, J, McArdle, CA, Melmed, S, Michel, MC, Miller, LJ, Mitolo, V, Mouillac, B, Mueller, CE, Murphy, P, Nahon, J-L, Ngo, T, Norel, X, Nyimanu, D, Ocarroll, A-M, Offermanns, S, Panaro, MA, Parmentier, M, Pertwee, RG, Pin, J-P, Prossnitz, ER, Quinn, M, Ramachandran, R, Ray, M, Reinscheid, RK, Rondard, P, Rovati, GE, Ruzza, C, Sanger, GJ, Schoeneberg, T, Schulte, G, Schulz, S, Segaloff, DL, Serhan, CN, Stoddart, LA, Sugimoto, Y, Summers, R, Tan, VP, Thal, D, Thomas, WW, Timmermans, PMWM, Tirupula, K, Tulipano, G, Unal, H, Unger, T, Valant, C, Vanderheyden, P, Vaudry, D, Vaudry, H, Vilardaga, J-P, Walker, CS, Wang, JM, Ward, DT, Wester, H-J, Willars, GB, Woodruff, TM, Yao, C, and Ye, RD

Abstract

The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15538. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.

Published
2021

21. Purinergic Signaling and Related Biomarkers in Depression

Author

Bartoli, F, Burnstock, G, Crocamo, C, Carra, G, Bartoli, F, Burnstock, G, Crocamo, C, and Carra, G

Abstract

It is established that purinergic signaling can shape a wide range of physiological functions, including neurotransmission and neuromodulation. The purinergic system may play a role in the pathophysiology of mood disorders, influencing neurotransmitter systems and hormonal pathways of the hypothalamic-pituitary-adrenal axis. Treatment with mood stabilizers and antidepressants can lead to changes in purinergic signaling. In this overview, we describe the biological background on the possible link between the purinergic system and depression, possibly involving changes in adenosine- and ATP-mediated signaling at P1 and P2 receptors, respectively. Furthermore, evidence on the possible antidepressive effects of non-selective adenosine antagonist caffeine and other purinergic modulators is reviewed. In particular, A2A and P2X7 receptors have been identified as potential targets for depression treatment. Preclinical studies highlight that both selective A2A and P2X7 antagonists may have antidepressant effects and potentiate responses to antidepressant treatments. Consistently, recent studies feature the possible role of the purinergic system peripheral metabolites as possible biomarkers of depression. In particular, variations of serum uric acid, as the end product of purinergic metabolism, have been found in depression. Although several open questions remain, the purinergic system represents a promising research area for insights into the molecular basis of depression.

Published
2020

25. Alterations in P2X and P2Y purinergic receptor expression in urinary bladder from normal cats and cats with interstitial cystitis

Author

Birder, L.A., Ruan, H.Z., Chopra, B., Xiang, Z., Barrick, S., Buffington, C.A., Roppolo, J.R., Ford, A.P.D.W., de Groat, W.C., and Burnstock, G.

Subjects
Cystitis -- Research, Biological sciences
Abstract

Alterations in P2X and P2Y purinergic receptor expression in urinary bladder from normal cats and cats with interstitial cystitis. Am J Physiol Renal Physiol 287: F1084-F1091, 2004. First published July 13, 2004; doi:10.1152/ajprenal.00118.2004.--Purinergic mechanisms appear to be involved in motor as well as sensory functions in the urinary bladder. ATP released from efferent nerves excites bladder smooth muscle, whereas ATP released from urothelial cells can activate afferent nerves and urothelial cells. In the present study, we used immunohistochemical techniques to examine the distribution of purinoceptors in the urothelium, smooth muscle, and nerves of the normal cat urinary bladder as well as possible changes in the expression of these receptors in cats with a chronic painful bladder condition termed feline interstitial cystitis (FIC) in which ATP release from the urothelium is increased. In normal cats, a range of P2X (P2[X.sub.1], P2[X.sub.2], P2[X.sub.3], P2[X.sub.4], P2[X.sub.5], P2[X.sub.6], and P2[X.sub.7]) and P2Y (P2[Y.sub.1], P2[Y.sub.2], and P2[Y.sub.4]) receptor subtypes was expressed throughout the bladder urothelium. In FIC cats, there is a marked reduction in P2[X.sub.1] and loss of P2[Y.sub.2] receptor staining. Both P2[X.sub.3] and P2[Y.sub.4] are present in nerves in normal cat bladder, and no obvious differences in staining were detected in FIC. Smooth muscle in the normal bladder did not exhibit P2Y receptor staining but did exhibit P2X (P2[X.sub.2], P2[X.sub.1]) staining. In the FIC bladder smooth muscle, there was a significant reduction in P2[X.sub.1] expression. These findings raise the possibility that purinergic mechanisms in the urothelium and bladder smooth muscle are altered in FIC cats. Because the urothelial cells appear to have a sensory function in the bladder, it is possible that the plasticity in urothelial purinergic receptors is linked with the painful bladder symptoms in IC. feline interstitial cystitis; ATP; urotbelium

Published
2004

37. ATP is released from guinea pig ureter epithelium on distension

Author

Knight, G.E., Bodin, P., De Groat, W.C., and Burnstock, G.

Subjects
Adenosine triphosphate -- Physiological aspects, Ureters -- Physiological aspects, Body fluids -- Pressure, Epithelial cells -- Physiological aspects, Exocytosis -- Physiological aspects, Biological sciences
Abstract

ATP is released from guinea pig ureter epithelium on distension. Am J Physiol Renal Physiol 282: F281-F288, 2002; 10.1152/ajprenal.00293.2001.--Distension of the perfused guinea pig ureter at pressures from 20 to 700 cm[H.sub.2]O increased the amount of ATP released from the epithelium in a pressure-dependent manner. During basal perfusion (40 [micro]l/ min), the perfusate contained 10 pmol/ml ATP; this increased 10- to 50-fold at various distending pressures. ATP was released from epithelial cells during distension as mechanical removal of the urothelium blocked release. No lactate dehydrogenase was detected in the perfusate, and scanning electron microscopy confirmed an intact urothelium after distension. ATP was not released due to the activation of stretch-activated channels, as gadolinium (10 [micro]M) failed to affect ATP release. Glibenclamide (10 [micro]M), known to inhibit two members of the ATP-binding cassette (ABC) protein family, did not affect ATP release after distension; nor did verapamil (10 [micro]M). In contrast, both monensin (100 [micro]M) and brefeldin A (10 [micro]M), which interfere with vesicular formation or trafficking, inhibited distension-evoked ATP release, which was [Ca.sup.2+]-dependent. This suggests that ATP release from the ureter epithelium might be mediated by vesicular exocytosis. The role of ATP released by distension of hollow visceral organs is discussed in relation to the concept of purinergic mechanosensory transductions, with special reference to nociception and the activation of P2[X.sub.3] receptors on the subepithelial sensory nerves. adenosine 5'-triphosphate; luciferin-luciferase; nociception; urothelium; vesicular exocytosis

Published
2002

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