Subtypes of .ALPHA.1-Adrenoceptors Involved in Noradrenaline-Induced Contractions of Rat Thoracic Aorta and Dog Carotid Artery.

Abstract

ABSTRACT-We tried to determine a 1-adrenoceptor subtypes involved in nor adrenaline-induced contractions of rat thoracic aorta and dog carotid artery. Prazosin competitively antagonized the contractions induced by noradrenaline in both the arter ies with a high pKB value (approximately 9.7). WB4101, benoxathian, phentolamine, HV723 and 5-methylurapidil also competitively antagonized the responses to noradrena line in both the arteries: however, the affinities for the antagonists were significantly higher in the rat thoracic aorta than in the dog carotid artery. The affinities for the competitive antagonists were not changed by treatment with nifedipine. In the rat thoracic aorta, chlorethylclonidine (CEC) elicited either a persistent contraction with rhythmic activities before treatment with nifedipine or partial inactivation of a 1-adre noceptors in the presence of nifedipine. On the other hand, CEC produced only in activation of a 1-adrenoceptors in the dog carotid artery. These results suggest that noradrenaline-induced contractions of the rat thoracic aorta and dog carotid artery are respectively mediated through distinct a 1-adrenoceptor subtypes. According to the a 1A, a113 subclassification, the a 1-adrenoceptor of dog carotid artery is like the a113 subtype, while that of rat thoracic aorta is atypical. Both subtypes are also identified as a high affinity site for prazosin (a 1H subtype) in the a 1H, a 1L and a 1N subclassifica tion.Contractile responses to noradrenaline in various blood vessels are antagonized by pra zosin or other a-adrenoceptor antagonists with different affinities (1-4). Recent functional studies have revealed that the various affinities for a given a-adrenoceptor antagonist among blood vessels reflect the presence of distinct a 1-adrenoceptor subtypes involved in the noradrenaline-induced contractions (4-8). At present, two different a 1-adrenoceptor sub classifications have been proposed. The a 1A and a113 subclassification was developed from binding studies, where WB4101, benoxathian, phentolamine and 5-methylurapidil show high er affinity for the a 1A subtype than the a113 subtype and CEC selectively inactivates the a113 subtype (9-12). However, prazosin can not discriminate between a 1A and a113 sub types. On the other hand, the a 1H, a 1L and a IN subclassification was originally derived from functional studies, in which prazosin and HV723 are pharmacological probes to distin guish the three subtypes (4, 13). The a 1H sub type has high affinity for prazosin, while the a IL and a IN subtypes have lower affinity for prazosin. HV723 is a highly selective antago

Investigation of the actions of chloroethylclonidine in rat aorta

“…However, whereas Nunes & Guimaraes (1993) found that CEC contracted the dog saphenous vein with a maximum response approximately 75% of that to phenylephrine, the present study of rat aorta found no contractile response to CEC alone. Although most studies of rat aorta report no direct contraction to CEC (see Introduction), direct contractions were reported in one study (Muramatsu et al, 1991) and were found to be nifedipine-sensitive. In our studies, clear contractile responses to CEC were observed in only 3 experiments (Authors' unpublished observations).…”

“…The conBritish Journal of Pharmacology (1995Pharmacology ( ) 115, 1399Pharmacology ( -1406 tractile response of rat aorta to NA following CEC pretreatment has been reported to be resistant to a-adrenoceptor antagonism (Oriowo & Bevan, 1990;Oriowo & Ruffolo, 1992). In one study, CEC also produced direct contractions of the smooth muscle (Muramatsu et al, 1991). In other tissues, CEC has been reported to be an irreversible agonist at a2-adrenoceptors, both prejunctionally (Bultmann & Starke, 1993) and postjunctionally (Nunes & Guimaraes, 1993).…”

(−)‐Discretamine, a selective α1D‐adrenoceptor antagonist, isolated from Fissistigma glaucescens

“…Among them, the olc-adrenoceptor is not present in any rat tissue . The subtype of al-adrenoceptor present in the rat aorta has been variously classified as MIB (Han et al, 1990), both alp and XIB (Tian et al, 1990;Piascik et al, 1991) or atypical (Muramatsu et al, 1991;Aboud & Docherty, 1992;Oriowo & Ruffolo, 1992 (Perez et al, 1991). The al-adrenoceptor subtypes possess different susceptibilities to 5-methyl-urapidil (5-MU), and CEC.…”

“…(Muramatsu et al, 1991;Aboud & Docherty, 1992;Oriowo & Ruffolo, 1992). In the last three studies, CEC failed to reduce the maximum response to NA, but caused a parallel shift in the concentration-response curve.…”

Investigation of the subtypes of α1‐adrenoceptor mediating contractions of rat aorta, vas deferens and spleen

“…The subtype of ol-adrenoceptor present in the rat aorta has been variously classified as aeB (Han et al, 1990) both MIA and O1B (Tian et al, 1990;Piascik et al, 1991) or atypical (Muramatsu et al, 1991;Aboud & Docherty, 1992;Oriowo & Ruffolo, 1992). In the latter four studies, CEC failed to SUBTYPES OF SMOOTH MUSCLE ot1-ADRENOCEPTORS 81 reduce the maximum response to NA, but caused a parallel shift in the concentration-response curve.…”