Table 7

P2 receptor signal transduction mechanisms, agonists, and antagonists

Receptor typeIon channelG protein-coupled: Gq/11, Gi 7-b
Nonselective pore7-a
Signaling pathwayN.A.PLC, AC,7-c K+ channels7-d
PLCPC,7-e PLA2,7-fPLD7-f
EffectorsCa2+ ≫ Na+ > K+ ↑IP3, ↑Ca2+, ↑DAG
Ca2+, Cl, K+ currents7-h
Agonists Nonselective ATPATP7-i
P2X/P2Y-selective α,β-meATP7-l ADP7-c
β,γ-meATP7-l UTP7-m
BzATP7-a UTPγS7-j
Antagonists Nonselective SuraminSuramin
Reactive blue 2Reactive blue 2
P2X/P2Y-selective NF023ARL 670857-o
NF279FPL 660967-o
KN-627-a A3P5PS7-k
MRS 21797-k
  • N.A., not applicable.

  • 7-a P2X7 and endogenous P2X7-like receptor.

  • 7-b P2Y1 and endogenous P2Y1-like receptors acting through PLC couple to Gq/11 proteins; P2Y1 and endogenous P2Y1-like receptors acting through adenylate cyclase couple to Gi proteins; P2Y2 and endogenous P2Y2-like receptors, P2Y4 and P2Y ADPreceptors couple to Gq/11 and Gi proteins; p2y3 and P2Y6 receptors couple to Gq/11 proteins.

  • 7-c P2Y1 and endogenous P2Y1-like receptors andP2Y ADP receptors.

  • 7-d Some endogenous P2Y1-like receptors activate K+ channels via interactions with their G protein subunits.

  • 7-e P2Y1 and endogenous P2Y1-like receptor signaling; possibly downstream of PKC.

  • 7-f P2Y1 and P2Y2 receptors and their endogenous counterparts; signaling possibly downstream of PKC.

  • 7-g P2Y1 and P2Y2 receptors and their endogenous counterparts; signaling downstream of PKC.

  • 7-h Secondary to activation of PLC, although activation of K+ currents by some endogenous P2Y1-like receptors is via direct interactions with G protein subunits.

  • 7-i P2Y1 and P2Y2 receptors and their endogenous counterparts; ATP is an antagonist at P2Y ADPreceptors.

  • 7-j P2Y2 and endogenous P2Y2-like receptors.

  • 7-k P2Y1 and endogenous P2Y1-like receptors.

  • 7-l P2X1, P2X3 and heteromeric P2X2P2X3 receptors.

  • 7-m P2Y2 and endogenous P2Y2-like receptors and P2Y4 receptors.

  • 7-n P2Y6 receptor.

  • 7-o P2Y ADP.

  • 7-p P2Y1 and endogenous P2Y1-like receptors coupled to AC.

  • Abbreviations: AC, adenylate cyclase; ADPβF, adenosine 5′-O-(2-fluoro)-diphosphate; ADPβS, adenosine 5′-O-(2-thio-diphosphate; cAMP, adenosine 3′,5′-cyclic monophosphate; A3P5PS, adenosine 3′-phosphate 5′-phosphosulfate; ARL 67085, 6-N,N-diethyl-D-β,γ-dibromomethylene ATP; ATPγS, adenosine 5′-O-(3-thiotriphosphate); BzATP, 3′-O-(4-benzoyl)benzoyl ATP; DAG, diacylglycerol; FPL 66096, 2-propylthio-D-β,γ-difluoromethylene ATP; IP3, inositol 1,4,5-trisphosphate; KN-62, 1-[N,O-bis(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine; MAPK, mitogen-activated protein kinase; α,β-meATP, α,β-methylene ATP; β,γ-meATP, β,γ-methylene ATP; 2MeSADP, 2-methylthio ADP; 2MeSATP, 2-methylthio ATP; MRS 2179, N6-methyl modification of 2′-deoxyadenosine 3′,5′-bisphosphate; NF023, symmetrical 3′-urea of 8-(benzamido)naphthalene-1,3,5-trisulfonic acid; NF279, 8,8′-(carbonylbis(imino-4,1-phenylenecarbonylimino-4,1-phenylenecarbonylimino))bis(1,3,5-naphthalenetrisulfonic acid); PLCPC, phosphatidylcholine-specific phospholipase C; PKC, protein kinase C; PLA2, phospholipase A2; PLC, phospholipase C; PLD, phospholipase D; PPADS, pyridoxal phosphate-6-azophenyl-2′,4′-disulfonic acid; suramin, 8-(3-benzamido-4-methylbenzamido)-naphthalene-1,3,5-trisulfonic acid; UTPγS, uridine 5′-O-(3-thiotriphosphate).