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

Y.P. Jarajapu, Paul Coats, John C. McGrath, Chris Hillier, Allan MacDonald

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29 Citations (Scopus)

Abstract

alpha (1)-adrenoceptor subtypes in human skeletal muscle resistance arteries were characterized using agonists noradrenaline (non-selective) and A61603 (alpha (1A)-selective), the antagonists prazosin (non-selective), 5-methyl-urapidil (alpha (1A)-selective) and BMY7378 (alpha (1D)-selective) and the alkylating agent chloroethylclonidine (Dreferential for alpha (1B)).
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 pA(2) value of 9.18, consistent with the presence of alpha (1)-adrenoceptors, although the Schild slope (1.32) was significantly different from unity.
5-Methyl-urapidil competitively antagonized responses to noradrenaline with a pK(B) value of 8.48 and a Schild slope of 0.99, consistent with the presence of alpha (1A)-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 muM chloroethylclonidine suggesting the absence of alpha (1B)-adrenoceptors. Maximum responses to noradrenaline and A61603 were reduced to a similar extent by 10 muM chloroethylclonidine, suggesting an effect of chloroethylcionidine at alpha (1A)-adrenoceptors at the higher concentration.
BMY7378 (10 and 100 nM) had no effect on responses to noradrenaline. BMY7378 (1 muM) poorly shifted the potency of noradrenaline giving a pA(2) of 6.52. These results rule out the presence of the alu-subtype.
These results show that contractile responses to noradrenaline in human skeletal muscle resistance arteries are predominantly mediated by the alpha (1A)-adrenoceptor subtype with a minor population of an unknown alpha (1)-adrenoceptor subtype.
Original languageEnglish
Pages (from-to)679-686
Number of pages8
JournalBritish Journal of Pharmacology
Volume133
Issue number5
DOIs
Publication statusPublished - Jul 2001

Keywords

  • alpha(1)-adrenoceptor subtypes
  • human
  • skeletal muscle resistance arteries

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