Receptors for purines and pyrimidines

V Ralevic, G Burnstock - Pharmacological reviews, 1998 - ASPET
V Ralevic, G Burnstock
Pharmacological reviews, 1998ASPET
Extracellular purines (adenosine, ADP, and ATP) and pyrimidines (UDP and UTP) are
important signaling molecules that mediate diverse biological effects via cellsurface
receptors termed purine receptors. In this review particular emphasis is placed on the
discrepancy between the pharmacological properties of native and recombinant receptors
for these agents. There are two main families of purine receptors, adenosine or P1
receptors, and P2 receptors, recognizing primarily ATP, ADP, UTP, and UDP. Adenosine/P1 …
Extracellular purines (adenosine, ADP, and ATP) and pyrimidines (UDP and UTP) are important signaling molecules that mediate diverse biological effects via cellsurface receptors termed purine receptors. In this review particular emphasis is placed on the discrepancy between the pharmacological properties of native and recombinant receptors for these agents. There are two main families of purine receptors, adenosine or P1 receptors, and P2 receptors, recognizing primarily ATP, ADP, UTP, and UDP. Adenosine/P1 receptors have been further subdivided, according to convergent molecular, biochemical, and pharmacological evidence into four subtypes, A1, A2A, A2B, and A3, all of which couple to G proteins. Based on differences in molecular structure and signal transduction mechanisms, P2 receptors divide naturally into two families of ligandgated ion channels and G protein-coupled receptors termed P2X and P2Y receptors, respectively; to date b Abbreviations: ACh, acetylcholine; ADP, adenosine 5!-diphosphate; AMP, adenosine 5!-monophosphate; ANAPP3, arylazidoaminopropionyl ATP; Ap3A, P1, P3-diadenosine triphosphate; Ap4A, P1, P4-diadenosine tetraphosphate; Ap5A, P1, P5-diadenosine pentaphosphate; Ap6A, P1, P6-diadenosine hexaphosphate; APEC, 2-[(2-aminoethylamino) carbonylethylphenylethylamino]-5!-N-ethylcarboxamido adenosine; APNEA, N-[2-(4-aminophenyl) ethyl] adenosine; ATP, adenosine 5!-triphosphate; A3P5P, adenosine-3!-phosphate-5!-phosphosulfate; ATPS, adenosine 5!-O-(3-thiotriphosphate); BzATP, 3!-O-(4-benzoyl) benzoyl ATP; cAMP, adenosine 3!, 5!-cyclic monophosphate; CGRP, calcitonin gene-related peptide; CGS 21680, 2-[p-(2-carbonyl-ethyl)-phenylethylamino]-5!-N-ethylcarboxamidoadenosine; CHO, chinese hamster ovary; CNS, central nervous system; CPA, N6-cyclopentyladenosine; DIDS, 4, 4!-diisothiocyanatostilbene-2, 2!-disulfonate; DPCPX, 1, 3-dipropyl-8-cyclopentylxanthine; EDRF, endothelium-derived relaxing factor; EDHF, endothelium-derived hyperpolarizing factor; GRK, G protein-coupled receptor specific kinase; IB-MECA, N6-(3-iodobenzyl)-5!-(N-methylcarbamoyl) adenosine; IP3, inositol 1, 4, 5-trisphosphate; KFM 19,()-8-(3-oxocyclopentyl)-1, 3-dipropylxanthine; MAPK, mitogen-activated protein kinase;,-meATP,,-methylene ATP;,-meATP,,-methylene ATP; 2Me-SATP, 2-methylthio ATP; mRNA, messenger RNA; NECA, N-ethylcarboxamidoadenosine; NF023, symmetrical 3!-urea of 8-(benzamido) naphthalene-1, 3, 5-trisulfonic acid; PKC, protein kinase C; PLA2, phospholipase A2; PLC, phospholipase C; PLD, phospholipase D; PNS, peripheral nervous system; PPADS, pyridoxalphosphate-6-azophenyl-2!, 4!-disulfonic acid; R-PIA,(R) N6-phenylisopropyl adenosine; RNA, ribonucleic acid; SCG, superior cervical ganglion; suramin, 8-(3-benzamido-4-methylbenzamido)-naphthalene-1, 3, 5-trisulfonic acid; 8-SPT, 8-(p-sulfophenyl) theophylline; TM, transmembrane; UDP, uridine 5!-diphosphate; UTP, uridine 5!-triphosphate; XAC, xanthine amine congener.
ASPET