TABLE 4.

Reported P₂ purinoceptors^*

Name	P2x	P2Y	P2U	P2T	P2Z	P2D
Structure (known)	No	Yes†	Yes‡	No	No	No
Molecular mass
(aa)			373‡
(kDa)		42†	42	43§
Type	Intrinsic ion channel ║	G-protein-coupled ¶	G-protein-coupled#	G-protein-coupled	Nonselective pore	G-protein coupled?
Effectors	Na+, K+, Ca2+	↑IP3/Ca2+/DAG; ↓cAMP, ↑phos- pholipase A2(↓K+-conduct- ance††	IP3/Ca2+/DAG; Ca2+, CI, and K+ currents	IP3/Ca2+/DAG; cAMP	Na+, K+, Ca2+	↑Ca2+**
Agonist	αβ-MeATP ≥ βγ- MeATP > ATP ≥ ADP > 2MeSATP >> UTP‡‡	2-MeSATP > ATP = ADP >> αβ MeATP >> UTP§§	UTP ≥ ATP = ATPγS >> 2- MeSATP = αβ- MeATP║║	2-substituted ADP > ADP¶¶	ATP4−	AP4A > ADPβS > AMP-PNP> Ap5A > αβ MeATP >> 2- MeSATP
Antagonist	Desensitization## by αβ-MeATP ANAPP3 Suramin*** (pKB = 5.0) PPADS††	Suramin (pA2 5.0)‡‡‡	None known§§§	ATP (pA2 = 4.6)║║║ Suramin (pA2 = 4.6)¶¶¶, ### FPL 66096 (pKB = 8.7)###		None known
Radioligand	[3H]D-αβ-MeATP (PKH = 9.0;pKL = 7.0****	[35S]ADPβS (af- finity: pKd = 8.0)††††		β[32P]2-MeSADP (pKd = 8.0)‡‡‡‡ [35S]ATPαS (pKd = 8.5)§§§§		[3H]AP4A (1 × 10−10 M; 0.6 MM)║║║║
Distribution	Smooth muscles, brain, heart, spleen¶¶¶¶	Wide distribu- tion####	Wide. Found in many cultured cells and in vas- cular muscle	Platelets	Mast cells,***** macrophages, vas defer- ens†††††	Chromaffin cells, rat brain synap- tosomes

^*Abbreviations: IP₃, inositol triphosphate; DAG, diacylglycerol; Me, methyl; cAMP, cyclic AMP; PNP, AP₄A, diadenosine tetraphosphate; Ap₅A, diadenosine pentaphosphate; ANAPP₃, arylazido aminopropionyl ATP.

^†Webb et al. (1993).

^‡Lustig et al. (1993).

^§Determined by photoaffinity labeling using 2-(p-axidophenyl)-ethylthioadenosine 5′-diphosphate (Cristalli and Mills, 1993).

^║Benham and Tsien (1987), Dubyak (1991), Bean (1992).

^¶Responses to P_2Y receptors are often, but not always, blocked by pertussis toxin indicating involvement of G_i/G_o proteins. Often (Bruner and Murphy, 1993) pertussis toxin affords a partial blockade indicating involvement of also G_q/G₁₁ proteins. In some instances (e.g., C6-2B glioma cells) the response (↓ cyclic AMP) is fully pertussis toxin sensitive.

^#P_2U receptor-mediated responses are often only partially blocked by pertussis toxin, suggesting that they are mediated by both G_i/G_o and by G_q/G₁₁ proteins (Gerwins and Fredholm, 1992).

^**The increase in [Ca²⁺]_i appears to be via mobilization of intracellular stores (Castro et al., 1992).

^††Shen and North (1993); Dubyak, 1991; Boyer et al., 1993.

^‡‡There are some minor differences between the potency order as determined in functional assays (e.g., rabbit ear artery, O’Connor et al., 1990) and in binding assays (Bo and Burnstock, 1992). The channel activity studied by patch-clamp is somewhat different in that ATP is equipotent with αβ-MeATP and βγ-MeATP (Bean, 1992).

^§§Important differences have been noted. For relaxation of rat pulmonary vessels the potency order (relative to that of the most potent compound in the series) was 2-MeSATP (1) > ATP (0.02) = ADP (0.02) > βγ-MeATP (0.01) > αβ-MeATP (0.006) (Liu et al., 1989); responses to activation of the cloned P_2Y1 receptor showed the order 2-MeSATP (1) = ATP (1) > ADP (0.05) >> αβ-MeATP, whereas binding to turkey erythrocytes shows the order 2-MeSATP (1) > ATP (0.1) ≥ ADP (0.07) > αβ-MeATP (0.002) > βγ-MeATP (0.0006) (Cooper et al., 1989).

^║║UTP is sometimes considerably more potent than ATP (van Rhee et al., 1993).

^¶¶Cusack and Hourani (1981; 1982a), MacFarlane (1983), Greco et al. (1991).

^##Desensitization is often rapid and may be irreversible, especially with photoactivated ANAPP₃ (Hogaboom et al., 1980; Kasakov and Burnstock, 1983).

^***Leff et al. (1990).

^†††Ziganshin et al (1993).

^‡‡‡Hoyle et al. (1990).

^§§§There are reports that suramin is (van der Zee et al., 1992) and is not (Wilkinson et al., 1993) an antagonist.

^║║║Cusack and Hourani (1982b).

^¶¶¶Hourani et al. (1992).

^###2-Propylthio-d-β,γ-difluoromethylene ATP (Humphries et al., 1993).

^****Bo and Burnstock (1990).

^††††Cooper et al. (1989).

^‡‡‡‡MacFarlane et al. (1983).

^§§§§Greco et al. (1991).

^║║║║High-affinity sites represent less than half the total binding sites (Pintor et al., 1993). The second set of figures within parentheses are K_i values for a low affinity site.

^¶¶¶¶Contractile responses in smooth muscle have been well characterized, e.g., in rabbit mesenteric artery (Burnstock and Warland, 1987) and rabbit ear artery (O’Connor et al., 1990). Binding has been studied, e.g., in rat bladder, brain, heart, vas deferens, and spleen (Bo and Burnstock, 1990; Michel et al., 1993). ATP-induced channel activity has been studied, e.g., in PC12 cells, but this probably is a secondary event (Nakazawa et al., 1991), sensory neurons (Krishtal et al., 1983; Bean et al., 1990) and ear artery muscle (Benham and Tsien, 1987).

^####Functional responses have been studied, e.g., in guinea pig aorta (Dainty et al., 1992) and in turkey erythrocytes (Berrie et al., 1989). Binding has been studied in turkey erythrocytes (Cooper et al., 1989).

^*****Dahlqvist and Diamant (1974), Steinberg and Silverstein (1987).

^{†††††}Fedan et al. (1990).