Evidence for and against heterogeneity of alpha1-adrenoceptors

Hieble, J. Paul; DeMarinis, Robert M.; Matthews, William D.

doi:10.1016/0024-3205(86)90466-2

Cited by 47 publications

(22 citation statements)

References 51 publications

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“…Contractile responses to noradrenaline in various blood vessels are antagonized by pra zosin or other a-adrenoceptor antagonists with different affinities (1)(2)(3)(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)(5)(6)(7)(8).…”

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

1991

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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

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

1991

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“…There is increasing evidence that their heterogeneity is related to pharmacologically distinct aL-adrenoceptor subtypes which may be linked to different second messenger systems (McGrath, 1982;Hieble et al, 1986;Han et al, 1987a;Johnson & Minneman, 1987;McGrath & Wilson, 1988). Drew (1985) noted that a1-adrenoceptors of various isolated tissues showed a wide variation in their affinities for yohimbine and prazosin, and Flavahan & Vanhoutte (1986) suggested that there were two distinct subtypes of al-adrenoceptors which could be distinguished by their affinities for both prazosin and yohimbine in the blood vessels (x1H and ClL according to their High or Low affinity for prazosin).…”

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Pharmacological subclassification of α₁‐adrenoceptors in vascular smooth muscle

Muramatsu

Ohmura

Kigoshi

et al. 1990

British J Pharmacology

284

179

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1 We examined whether x1-adrenoceptors in various blood vessels can be divided into subtypes by antagonist affinity or by susceptibility to chloroethylclonidine or nifedipine. 2 Noradrenaline or phenylephrine produced concentration-dependent contractions in all the tissues tested, which were competitively inhibited by phentolamine, yohimbine, prazosin, WB4101 and HV723. However, there were large differences between the tissues in the pA2 values for all the antagonists except phentolamine. 3 The blood vessels could be classified into three groups (I, II and III) on the basis of their affinity variation. In group I (dog mesenteric artery and vein, saphenous vein), the pA2 values for HV723 were greater than 9, and those for HV723 and WB4101 were approximately 1 log unit higher than for prazosin.This rank order of affinity reversed in group II (dog carotid artery and rat thoracic aorta), where prazosin was more potent (pA2 values greater than 9.5) than HV723 or WB4101. In group III (rabbit mesenteric artery, thoracic aorta and carotid artery and guinea-pig thoracic aorta), on the other hand, prazosin, HV723 and WB4101 inhibited the noradrenaline response with a similar affinity (pA2 values ranging from 8 to 9). 4 Yohimbine inhibited the responses to noradrenaline and phenylephrine with a lower affinity than prazosin, HV723 or WB4101. The pA2 values for yohimbine were similar in groups I and II (the values greater than 6.5), which were greater than those in group III (values less than 6.4).5 The al-adrenoceptors in group II were selectively affected by chlorethylclonidine, resulting in an irreversible attenuation of noradrenaline responses in the dog carotid artery and a persistent contraction in the rat thoracic aorta.6 Nifedipine either produced no effect or a slight inhibition of al-adrenoceptor-mediated contractions in all the blood vessels; these effects were not correlated to the above groups.7 These results suggest that a,-adrenoceptors of blood vessels can be divided into three subtypes (designated as a1H, 04L and a1N) by antagonist affinity and their susceptibility to chloroethylclonidine but not to nifedipine: the characteristics of each subtype are summarized in Table 3. Subtypes oelH, oL and UlN may be predominantly involved in the contractile responses to noradrenaline or phenylephrine of the blood vessels in groups II, III and I, respectively.

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“…Alternatively, it is possible that the differences reflect binding to related, but not identical, parts of the receptor active site, or perhaps even to different "subtypes" of the alpha-1 adrenergic receptor (Ruffolo et al, 1977). Although it is not possible at present to distinguish unequivocally between these possibilities, there is general agreement that the interaction of certain phenethylamines with the alpha-1 adrenergic receptor is distinctly different from the interactions of the imidazolines with the same receptor (Ruffolo et al, 1979a(Ruffolo et al, , 1980aHieble et al, 1986;Miller et al, 1980).…”

Section: Classification Of Alpha-l Adrenergic Receptor Agonistsmentioning

confidence: 99%

The alpha-1 Adrenergic Receptors

Ruffolo¹

1987

The Receptors

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All rights reservedNo part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise without written permission from the Publisher.Preface vii ology will allow alpha-l adrenergic receptors to be isolated and purified and their amino acid sequence to be identified. This will ultimately allow for the systematic subclassification of alpha-l adrenergic receptors and for their differential regulation to be studied in greater detail. These new advances are likely to take place within the next five years, and it is our intent for this review of alpha-l adrenergic receptor pharmacology to provide an accurate summary of the current state of knowledge relating to alpha-l adrenergic receptors, which we hope will serve as a foundation upon which to build a broader base of knowledge in the future.

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Evidence for and against heterogeneity of alpha1-adrenoceptors

Cited by 47 publications

References 51 publications

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

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

Pharmacological subclassification of α₁‐adrenoceptors in vascular smooth muscle

The alpha-1 Adrenergic Receptors

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Evidence for and against heterogeneity of alpha1-adrenoceptors

Cited by 47 publications

References 51 publications

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

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

Pharmacological subclassification of α1‐adrenoceptors in vascular smooth muscle

The alpha-1 Adrenergic Receptors

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Pharmacological subclassification of α₁‐adrenoceptors in vascular smooth muscle