Table 7

P2 receptor signal transduction mechanisms, agonists, and antagonists

Family		P2X	P2Y
Receptor type		Ion channel	G protein-coupled: G_q/11, G_i ^7-b
		Nonselective pore^7-a
Signaling pathway		N.A.	PLC, AC,^7-c K⁺ channels^7-d
			PLC_PC,^7-e PLA₂,^7-fPLD^7-f
			PKC
			MAPK^7-g
Effectors		Ca²⁺ ≫ Na⁺ > K⁺	↑IP₃, ↑Ca²⁺, ↑DAG
			↓cAMP^7-c
			Ca²⁺, Cl⁻, K⁺ currents^7-h
Agonists	Nonselective	ATP	ATP^7-i
		ATPγS	ATPγS^7-j
		2MeSATP	2MeSATP^7-k
		Ap₄A	Ap₄A^7-j
	P2X/P2Y-selective	α,β-meATP^7-l	ADP^7-c
		β,γ-meATP^7-l	UTP^7-m
		BzATP^7-a	UTPγS^7-j
			UDP^7-n
			2Cl-ADP^7-c
			2MeSADP^7-c
			ADPβS,^7-cADPβF^7-c
Antagonists	Nonselective	Suramin	Suramin
		PPADS	PPADS
		Reactive blue 2	Reactive blue 2
	P2X/P2Y-selective	NF023	ARL 67085^7-o
		NF279	FPL 66096^7-o
		KN-62^7-a	A3P5PS^7-k
			MRS 2179^7-k
			2-hexylthio-ATP^7-p
			2-cyclohexylthio-ATP^7-p

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 G_q/11 proteins; P2Y₁ and endogenous P2Y₁-like receptors acting through adenylate cyclase couple to G_i proteins; P2Y₂ and endogenous P2Y₂-like receptors, P2Y₄ and P2Y _ADPreceptors couple to G_q/11 and G_i proteins; p2y3 and P2Y₆ receptors couple to G_q/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); PLC_PC, 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).