fold less potent. AH23848B (30 pM) and AH6809 (1 and 10 gM) caused no significant shift in the location of PGE2 E/[A] curves. 7 These data suggest that the rabbit isolated saphenous vein contains prostanoid, EP-, DP-, IP-and TP-receptors. Based on antagonist affinity information and agonist potency orders, the rabbit saphenous vein contains an inhibitory prostanoid EP-receptor different from that in the rabbit ear artery, but comparable to the recently described EP4-receptor.

1 The present study attempted to classify pharmacologically the a 1 -adrenoceptor subtype(s) present in two isolated, vascular ring preparations, the rabbit ear artery and rat thoracic aorta. 2 In the ear artery, the agonist e ects of phenylephrine were antagonized by 5-methyl urapidil (pA 2 =7.90; Schild slope=0.85) and BMY 7378 (pA 2 =6.11; Schild slope=0.80) but not in a simple competitive manner. The shallow Schild slopes are consistent with the activation of a heterogeneous receptor population. Indeed the 5-methyl urapidil data set could be ®tted to a two-receptor model yielding a high antagonist a nity (pK BH ) estimate of 7.85 and a low a nity (pK BL ) estimate of 6.03.3 The e ects of clonidine in the ear artery were competitively antagonised by 5-methyl urapidil (pK B =7.91) and BMY 7378 (pK B =5.53). These data are consistent with contractions to clonidine being mediated by a single receptor subtype. 4 In the aorta, the e ects of phenylephrine were antagonized by 5-methyl urapidil (pA 2 =7.95; Schild slope=1.11) and BMY 7378 (pA 2 =9.08; Schild slope=0.73). Neither data set was consistent with a simple competitive interaction. The BMY 7378 data suggested again, that phenylephrine was acting at a heterogeneous receptor population. Subsequent analysis by the two-receptor model yielded a high a nity (pK BH ) estimate of 8.95 and a low a nity (pK BL ) estimate of 7.00. 5 The alkylating agent, chloroethylclonidine (CEC) elicited concentration-dependent contractions in the ear artery with a potency (p[A] 50 ) of 5.57. Pretreatment of this tissue with CEC (5 mM, 30 min incubation) had no e ect on subsequent responses to phenylephrine. In contrast, in the aorta, CEC demonstrated no agonism but pretreatment with this agent (5 mM, 15 min incubation) caused a rightward shift and depression of subsequent phenylephrine concentration-e ect curves. 6 The a nity of clonidine in the rabbit ear artery (pK A =6.17) was found to be signi®cantly di erent to its a nity in the rat thoracic aorta (pK A =7.12) suggesting that this agonist activates di erent a 1 -adrenoceptor subtypes in the two tissues. 7 These results suggest that heterogeneous populations of a 1 -adrenoceptors are present in both tissues. In the ear artery, the pro®le of antagonist and agonist activity is most consistent with a 1A -adrenoceptors being the predominant receptor subtype. The second receptor population does not appear to correspond to any of the recognized a 1 -adrenoceptor subtypes. In the aorta a 1D -adrenoceptors appear to predominate, with a 1A -adrenoceptors being the most likely candidate for the second receptor population.

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1 The aim of this study was to determine the receptor profile of 9all1i-prostaglandin F2 (PGF2) and compare it with that of its parent, prostaglandin D2 (PGD2 I-PGF2 and PGD2 (10pM) were without affinity at the IP receptors on human platelets and had no agonist action in the EP3 receptor containing preparation, guinea-pig vas deferens. 6 9ax1 1,-PGF2 is a major metabolite of PGD2 in vivo and this conversion clearly represents an inactivation step since 9aIllfl-PGF2 is of considerably lower potency than PGD2 at DP receptors. However, it is of similar potency to PGD2 at TP, FP, EP1 and EP2 receptors and it may, therefore, contribute to the biological effects which follow PGD2 administration or endogenous synthesis; its actions at these receptors are likely to be similar to those of PGD2 itself.

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