Functional characterization of alpha(1)-adrenoceptor subtypes in human skeletal muscle resistance arteries

Jarajapu, Y. P.R., Coats, P., McGrath, J. C. , Hillier, C. and MacDonald, A. (2001) Functional characterization of alpha(1)-adrenoceptor subtypes in human skeletal muscle resistance arteries. British Journal of Pharmacology, 133(5), pp. 679-686. (doi: 10.1038/sj.bjp.0704130) (PMID:11429392) (PMCID:PMC1572837)

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Abstract

α1-adrenoceptor subtypes in human skeletal muscle resistance arteries were characterized using agonists noradrenaline (non-selective) and A61603 (α1A-selective), the antagonists prazosin (non-selective), 5-methyl-urapidil (α1A-selective) and BMY7378 (α1D-selective) and the alkylating agent chloroethylclonidine (preferential for α1B). Small arteries were obtained from the non-ischaemic skeletal muscle of limbs amputated for critical limb ischaemia and isometric tension recorded using wire myography. Prazosin antagonized responses to noradrenaline with a pA2 value of 9.18, consistent with the presence of α1-adrenoceptors, although the Schild slope (1.32) was significantly different from unity. 5-Methyl-urapidil competitively antagonized responses to noradrenaline with a pKB value of 8.48 and a Schild slope of 0.99, consistent with the presence of α1A-adrenoceptors. In the presence of 300 nM 5-methyl-urapidil, noradrenaline exhibited biphasic concentration response curves, indicating the presence of a minor population of a 5-methyl-urapidil-resistant subtype. Contractile responses to noradrenaline were not affected by 1 μM chloroethylclonidine suggesting the absence of α1B-adrenoceptors. Maximum responses to noradrenaline and A61603 were reduced to a similar extent by 10 μM chloroethylclonidine, suggesting an effect of chloroethylclonidine at α1A-adrenoceptors at the higher concentration. BMY7378 (10 and 100 nM) had no effect on responses to noradrenaline. BMY7378 (1 μM) poorly shifted the potency of noradrenaline giving a pA2 of 6.52. These results rule out the presence of the α1D-subtype. These results show that contractile responses to noradrenaline in human skeletal muscle resistance arteries are predominantly mediated by the α1A-adrenoceptor subtype with a minor population of an unknown α1-adrenoceptor subtype.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McGrath, Professor John
Authors: Jarajapu, Y. P.R., Coats, P., McGrath, J. C., Hillier, C., and MacDonald, A.
College/School:College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:British Journal of Pharmacology
Publisher:Wiley
ISSN:0007-1188
ISSN (Online):1476-5381

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