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α1D-Adrenoceptors mediate nerve and agonist-evoked contractions in mouse vas deferens: evidence obtained from knockout technology

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Abstract:

Summary

1 It has been demonstrated that nerve-evoked contractions of the rat vas deferens involve α1D-adrenoceptors. Definitive evidence for a similar α1D-adrenoceptor-mediated response in mouse vas deferens has been more difficult to obtain. In this study, we have used α1D-adrenoceptor knockout (α1D-KO) mice to aid in the pharmacological characterization.

2 Mouse whole vas deferens was stimulated with a single pulse every 5 min. Once a stable response had been obtained, vehicle or antagonist was administered cumulatively at 5-min intervals and a response to stimulation obtained 5 min later. Cumulative concentration-response curves were also obtained for noradrenaline.

3 In vas deferens from α1D-KO mice, the contractile response to low concentrations of noradrenaline and the contractile response to a single stimulus were significantly reduced as compared to wild type (WT).

4 The α1D-adrenoceptor selective antagonist, BMY 7378, produced a concentration-dependent inhibition of single pulse-evoked contractions of vas deferens from WT and α1D-KO mice. BMY 7378 was significantly less potent in inhibiting stimulation-evoked contractions in vas deferens from α1D-KO mice.

5 It is concluded that α1D-adrenoceptors mediate a component of nerve- and agonist-evoked contractions of the vas deferens of WT mice.

Keywords: BMY 7378; RS 100329; mouse vas deferens; transgenic; α1D-adrenoceptors

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1474-8673.2008.00420.x

Affiliations: 1: Department of Physiology, Royal College of Surgeons in Ireland, 123 St Stephen’s Green, Dublin 2, Ireland 2: Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, Scotland 3: Department of Pharmacology, National Research Institute for Child Health and Development, Tokyo 157–8535, Japan 4: Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606–8501, Japan

Publication date: April 1, 2008

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