Receptors for Purines and Pyrimidines

Receptors for Purines and Pyrimidines

0031-6997/98/5003-0413$03.00/0 PHARMACOLOGICAL REVIEWS Vol. 50, No. 3 Copyright © 1998 by The American Society for Pharmacology and Experimental Therapeutics Printed in U.S.A. Receptors for Purines and Pyrimidines VERA RALEVICa AND GEOFFREY BURNSTOCK School of Biomedical Sciences (V.R.), Queen’s Medical Centre, University of Nottingham, Nottingham, England; Autonomic Neuroscience Institute (G.B.), Royal Free Hospital School of Medicine, London, England This paper is available online at http://www.pharmrev.org I. Introduction........................................................................... 415 A. Overview ....................................................................... 415 B. Historical perspective ............................................................ 416 II. Adenosine/P1 Receptors ................................................................ 418 A. Introduction..................................................................... 418 B. Structure ....................................................................... 419 C. Agonists ........................................................................ 420 D. Antagonists ..................................................................... 421 III. A1 receptor............................................................................ 421 A. Cloned A1 receptors.............................................................. 422 B. Signal transduction mechanisms .................................................. 422 C. Desensitization .................................................................. 423 D. Sensitization/up-regulation ....................................................... 424 E. Agonists ........................................................................ 424 F. Antagonists ..................................................................... 424 G. Distribution and biological effects ................................................. 424 IV. A2A receptor .......................................................................... 427 A. Cloned A2A receptors............................................................. 427 B. Signal transduction mechanisms .................................................. 427 C. Desensitization .................................................................. 428 D. Sensitization/up-regulation ....................................................... 428 E. Agonists ........................................................................ 428 F. Antagonists ..................................................................... 429 G. Distribution and biological effects ................................................. 429 V. A2B receptor .......................................................................... 431 A. Cloned A2B receptors............................................................. 431 B. Signal transduction mechanisms .................................................. 432 C. Desensitization .................................................................. 432 D. Agonists and antagonists ......................................................... 432 E. Distribution and biological effects ................................................. 433 VI. A3 receptor............................................................................ 433 A. Cloned A3 receptors.............................................................. 433 B. Signal transduction mechanisms .................................................. 434 C. Desensitization .................................................................. 434 D. Up-regulation ................................................................... 434 E. Agonists ........................................................................ 434 F. Antagonists ..................................................................... 435 G. Distribution and biological effects ................................................. 435 VII. Integrated effects of adenosine/P1 receptors .............................................. 436 VIII. P2 receptors........................................................................... 437 A. Introduction..................................................................... 437 B. Agonists ........................................................................ 439 C. Antagonists ..................................................................... 440 1. Suramin ....................................................................... 440 a Address for correspondence: Vera Ralevic, School of Biomedical Sciences, Queen’s Medical Centre, University of Nottingham, Notting- ham NG7 2UH, England. E-mail: [email protected] 413 414 RALEVIC AND BURNSTOCK 2. NF023 (symmetrical 39-urea of 8-(benzamido)naphthalene-1,3,5-trisulfonic acid) ...... 441 3. NF279 (8,89-(carbonylbis(imino-4,1-phenylenecarbonylimino-4,1- phenylenecarbonylimino))bis(1,3,5-naphthalenetrisulfonic acid)) ..................... 443 4. Pyridoxal-5-phosphate (P5P)..................................................... 443 5. PPADS (pyridoxalphosphate-6-azophenyl-29,49-disulfonic acid) ...................... 443 6. Iso-PPADS..................................................................... 444 7. Reactive blue 2................................................................. 444 8. Reactive red ................................................................... 444 9. Trypan blue.................................................................... 444 10. Evans blue..................................................................... 444 11. DIDS (4,49-diisothiocyanatostilbene-2,29-disulfonate) ............................... 444 12. Arylazidoaminopropionyl ATP (ANAPP3) ......................................... 445 13. 2-Alkylthio derivatives of ATP ................................................... 445 14. 59-p-Fluorosulfonyl benzoyladenosine ............................................. 445 IX. P2X receptors ......................................................................... 445 A. Structure ....................................................................... 445 B. Cloned P2X receptors ............................................................ 447 1. P2X1 receptor .................................................................. 447 2. P2X2 receptor .................................................................. 447 3. P2X3 receptor .................................................................. 448 4. P2X4 receptor .................................................................. 448 5. P2X5 receptor .................................................................. 448 6. P2X6 receptor .................................................................. 449 7. P2X7 receptor .................................................................. 449 C. Signal transduction mechanisms .................................................. 449 D. Desensitization .................................................................. 449 E. Agonists and antagonists ......................................................... 451 F. Distribution and biological effects ................................................. 453 1. Central nervous system (CNS) ................................................... 454 2. Sensory nerves ................................................................. 454 3. Peripheral nervous system (PNS) ................................................ 454 4. Smooth muscle ................................................................. 455 5. Blood cells ..................................................................... 456 X. P2X7 and endogenous P2X7-like (or P2Z) receptors ........................................ 456 A. Structure ....................................................................... 456 B. Cloned P2X7 receptors ........................................................... 456 C. Signal transduction mechanisms .................................................. 457 D. Desensitization .................................................................. 457 E. Agonists ........................................................................ 457 F. Antagonists ..................................................................... 457 G. Distribution and biological effects ................................................. 457 XI. P2Y receptors ......................................................................... 458 A. Structure ....................................................................... 458 XII. P2Y1 and endogenous P2Y1-like receptors ................................................ 459 A. Cloned P2Y1 receptors ........................................................... 459 B. Signal transduction mechanisms .................................................. 459 C. Desensitization .................................................................. 460 D. Agonists ........................................................................ 461 E. Antagonists ..................................................................... 461 F. Heterogeneity of P2Y1 and endogenous P2Y1-like receptors .......................... 461 G. Distribution and biological effects ................................................. 462 XIII. P2Y2 and endogenous P2Y2-like receptor................................................. 464 A. Cloned P2Y2 receptors ........................................................... 464 B. Signal transduction mechanisms .................................................. 464 C. Desensitization .................................................................

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