Antagonist selectivities at endogenous P2 receptors
| Tissue | Receptor9-a | Suramin | PPADS | P5P | RB2 | NF023 | References9-k |
|---|---|---|---|---|---|---|---|
| Rat vas deferens | P2X (P2X1) | pKB 5.5 | iso-PPADS9-b | pKB5.3–5.8 | pKB 5.89-c | pA2 5.9 | 1,2 |
| K d3.9 | K d 1.0 | 3 | |||||
| Rabbit vas deferens | P2X (P2X1) | pA2 5.1 | pA26.3 | pA2 5.2 | pA2 5.7 | 4,5 | |
| Guinea-pig vas deferens | P2X (P2X1) | Yes (NC) | pKB5.6 | 6,7 | |||
| Rat mesenteric bed | P2X (P2X1) | pA2 5.0 | pKB 6.4 | pA25.4 | pA2 5.5 | 5,8 | |
| Hamster mesenteric bed | P2X (P2X1) | pA2 5.3 | pA2 5.6 | 9 | |||
| Rabbit ear artery | P2X (P2X1) | pKB4.8 | pA2 6.4 | N.D. | 10–12 | ||
| Rabbit saphenous artery | P2X (P2X1) | pA2 4.8 | pA26.0 | pA2 5.7 | 9,11,12 | ||
| Rat renal vascular bed | P2X (P2X1) | Yes | pKB6.0 | Yes | 13 | ||
| Guinea-pig ileum submucosal arterioles | P2X (P2X1) | pKB 5.5 | pKB6.3 | 14 | |||
| Rabbit urinary bladder | P2X (P2X1) | pA2 6.3 | 15 | ||||
| Guinea-pig urinary bladder | P2X (P2X1) | pA2 5.1 | pA26.7 | 16 | |||
| Human urinary bladder | P2X (P2X1) | pKB 5.99-d | 17 | ||||
| Human saphenous vein | P2X (P2X1) | pKB4.8 | 18 | ||||
| Rat vagus nerve | P2X | pA25.9 | iso-PPADS9-e | pKB 5.3–5.4 | pKB4.969-c | 19,20 | |
| Guinea-pig taenia coli | P2Y (P2Y1) | pA2 5.0 | pA24.6–5.3 | pA2 4.2 | 9,21,22 | ||
| K d10.1 | K d 22–34 | 3 | |||||
| Rat duodenum | P2Y (P2Y1) | pA2 5.0 | pA25.1 | pA2 5.4 | pA2 4.3 | 5,11 | |
| Rat mesenteric bed | P2Y (P2Y1) | pA2 5.3 | pA25.5–6.0 | pA2 4.9 | 9,11,22,23 | ||
| Bovine aorta | P2Y (P2Y1) | pKB 5.5 | 24 | ||||
| Rat aorta | P2Y (P2Y1) | K d2–6 | K d 0.2–0.4 | K d0.5–0.8 | 25 | ||
| Turkey erythrocytes | P2Y (P2Y1) | Yes (NC) | pA2 5.9 | Yes (NC) | 26 | ||
| Bovine pulmonary artery EC | P2Y (P2Y1) | pA25.5 | pA2 6.3 | 27 | |||
| Rabbit thoracic aorta | 9 | ||||||
| +EC(ATP) | P2Y (P2Y1) | pA2 3.2–4.4 | Inactive | ||||
| −EC(ATP) | P2Y | Inactive | Inactive | ||||
| C6 glioma cells | 26,28 | ||||||
| ↑IP3 | P2Y (P2Y1) | pA24.4 | Yes (NC) | ||||
| ↓cAMP | P2Y (P2Y1) | Slight at 100 μM | Inactive at <100 μM | pA2 6.3 | |||
| Rat astrocytes | P2Y | Yes | IC50 0.9 | 29 | |||
| Mouse vas deferens | P2Y-like9-f | pKB5.3 | 30 | ||||
| Rat atria | P2Y-like9-g | pKB 5.1 | 31 | ||||
| Rat mesenteric bed | P2Y (P2Y2) | Inactive | Inactive | Inactive | 9,23 | ||
| Hamster mesenteric bed | P2Y (P2Y2) | pA24.9 | Inactive | 9 | |||
| Bovine aorta | P2Y (P2Y2) | Inactive | 24 | ||||
| Rat aorta | P2Y (P2Y2) | K d26–37 | K d 6.5 | 25 | |||
| Bovine pulmonary artery EC | P2Y (P2Y2) | pA24.4 | pA2 5.7 | 27 | |||
| C6 glioma | P2Y (P2Y2) | pA2 4.4 | 26 | ||||
| C2C12 myotubes | P2Y (P2Y2) | pA2 4.4 | 32 | ||||
| Rat astrocytes | P2Y (P2Y2) | Yes | IC507.2 | 29 | |||
| Rat neuroblastoma × glioma cells | P2Y (P2Y2) | IC50 40–60 | IC5020–30 | 33 | |||
| RAW 264.7 macrophages | P2Y (pyrimidinoceptor) | pA2 4.8 | Inactive | pA25.8 | 34 | ||
| Rat mesenteric arteries | P2Y (pyrimidinoceptor)9-h | Inactive | Inactive | Inactive | 22,23,35 | ||
| Rat superior cervical ganglion | P2Y (pyrimidinoceptor)9-i | Inactive | 36 | ||||
| Human platelets | P2Y (P2T) | pA24.6 | Yes9-j | 37,38 |
P2X1-like receptor-mediated responses were determined against the effects of α,β-meATP; P2Y1-like receptor-mediated responses were determined against the effects of ADPβS or 2MeSATP; P2Y2-like receptor-mediated responses were determined against the effects of UTP (in tissues in which ATP is approximately equipotent with UTP).
NC, noncompetitive; +EC, with endothelium; -EC, without endothelium.
↵9-a The likely cloned receptor counterparts of endogenous responses are indicated in parentheses.
↵9-b pKB 6.6 for iso-PPADS (Khakh et al., 1994).
↵9-c Cibacron blue.
↵9-d Suramin antagonized only the lower part of the α,β-meATP response curve (Palea et al., 1995).
↵9-e pKB 6.0 for iso-PPADS (Trezise et al., 1994c).
↵9-f Antagonism of ATPγS inhibition of [3H]NA overflow.
↵9-g Antagonism of ATP- and ATPγS-mediated inhibition of evoked [3H]NA overflow.
↵9-h Tested against contractions to UTP.
↵9-i Tested against depolarizations to UDP and UTP; responses to α,β-meATP and ATP were blocked.
↵9-j At high concentrations (>100 μM).
↵9-k References: 1, Khakh et al., 1994; 2, Trezise et al., 1994b; 3, Bültmann et al., 1996b; 4, Lambrecht et al., 1992; 5, Lambrechtet al., 1996; 6, McLaren et al., 1994; 7, Bailey and Hourani, 1995; 8, Windscheif et al., 1994; 9, Ziyal, 1997; 10, Leff et al., 1990; 11, Lambrecht, 1996; 12,Ziganshin et al., 1994b; 13, Eltze and Ullrich, 1996; 14,Galligan et al., 1995; 15, Ziganshin et al., 1993; 16, Usune et al., 1996; 17, Palea et al., 1995; 18, von Kügelgen et al., 1995; 19, Treziseet al., 1994b; 20, Trezise et al., 1994c; 21,Hoyle et al., 1990; 22, Windscheif et al., 1995a; 23, Ralevic and Burnstock, 1996a; 24, Wilkinson et al., 1994; 25, Hansmann et al., 1997; 26, Boyer et al., 1994; 27, Chen et al., 1996a; 28, Lin and Chuang, 1994; 29, Ho et al., 1995; 30, von Kügelgen et al., 1994; 31, von Kügelgen et al., 1995b; 32,Henning et al., 1993; 33, Reiser, 1995; 34, Chen et al., 1996c; 35, Lagaud et al., 1996; 36, Connolly and Harrison, 1995; 37, Hourani et al., 1992; 38, Windscheifet al., 1995b.