α 1A‐Adrenoceptor‐mediated contractile responses of the human vas deferens

K. Furukawa, D. J. Rosario, D. J. Smith, C. R. Chapple, T. Uchiyama, R. Chess‐Williams*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

44 Citations (Scopus)

Abstract

The predominant α‐adrenoceptor mediating contractions of the human vas deferens has been characterised in vitro by use of subtype selective antagonists. Responses of human epididymal vas deferens were obtained to phenylephrine in the presence of amine uptake inhibitors and propranolol. The effects of the α1‐adrenoceptor antagonists, 5‐methylurapidil, oxymetazoline, WB4101, prazosin and chloroethylclonidine were examined and also the L‐type calcium channel blocker, nifedipine. 5‐Methylurapidil, WB4101, oxymetazoli and prazosin acted as competitive antagonists of the responses to phenylephrine, yielding pA2 values of 8.8, 9.2, 7.7 and 8.8 respectively. All four antagonists produced Schild plots with slopes similar to unity and maximum responses to phenylephrine were not altered in the presence of any of the antagonists. Tamsulosin (1 nM) caused rightward shifts of phenylephrine concentration‐response curves yielding an apparent pKB value of 10.0. However, maximum responses were also reduced by 51% with this concentration of antagonist. Incubation of tissues with chloroethylclonidine (100 μM for 40 min) failed to alter responses significantly but the presence of nifedipine (1 μM) reduced maximum responses to phenylephrine by 32%. The high affinity of 5‐methylurapidil, oxymetazoline and WB4101, together with the failure of chloroethylclonidine to antagonize responses, indicate that the predominant α‐adrenoceptor mediating contraction of the human vas deferens has the characteristics previously described for the pharmacologically‐defined α1A‐adrenoceptor. The data are also consistent with those described for the cloned α1C‐adrenoceptor subtype thereby supporting the hypothesis that the two receptors are identical. The human vas deferens therefore represents a readily accessible preparation for functional studies of the human α1A‐adrenoceptor. 1995 British Pharmacological Society

Original languageEnglish
Pages (from-to)1605-1610
Number of pages6
JournalBritish Journal of Pharmacology
Volume116
Issue number1
DOIs
Publication statusPublished - 1 Jan 1995
Externally publishedYes

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