Pharmacological classification of α₁‐adrenoceptors mediating contractions of rabbit isolated ear artery: comparison with rat isolated thoracic aorta

Abstract

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.

Functional characterization of α1-adrenoceptor subtypes in the rabbit spleen

“…The potencies of tamsulosin and Rec 15/2739 were similar to values obtained in the rabbit urethra (Auguet et al 1995;Leonardi et al 1997), heart (Yang and Endoh 1996), prostate and ear artery (Leonardi et al 1997). Agonist-induced contractions are presumably mediated via α 1L -adrenoceptors in the urethra and prostate (Auguet et al 1995;Leonardi et al 1997) while α 1A -adrenoceptors mediated contractions in the heart (Yang and Endoh 1996) and ear artery (Fagura et al 1997). These results therefore showed that the low antagonist potencies reported for prazosin, WB 4101 and 5-methylurapidil did not arise from methodological artifacts.…”

Identification of α-1L Adrenoceptor in Rabbit Ear Artery

“…High pA 2 or pK B values for prazosin and tamsulosin but low affinity for KMD-3213, 5-methylurapidil, RS-17053, and BMY 7378 prove an involvement of ␣-1B AR subtype. Low affinity (pK B : 7.9 and 7.2) for 5-methylurapidil has also been reported in the contractile responses to phenylephrine and noradrenaline of rabbit ear artery (Fagura et al, 1997;Testa et al, 1997).…”

Hypotensive Effects of Eugenosedin-A with Serotonin, Alpha- and Beta-Adrenoceptor Antagonistic Activities in Spontaneously Hypertensive and Normotensive Rats

“…Since · 2 -adrenoceptors may be involved in contractions of rat aorta, Fujimoto and Itoh [17] pointed out that the · 2 -adrenoceptor agonist clonidine in the thoracic aorta produces contractile activity. But in some studies, clonidine was described as being able to activate the · 1 -adrenoceptor to contract blood vessels [43]. However, the possibility that the rat aorta contains a heterogeneous population of ·-adrenoceptors should not be excluded [17].…”