Document Detail

Alpha1-adrenoceptors are required for normal male sexual function.
MedLine Citation:
PMID:  17603545     Owner:  NLM     Status:  MEDLINE    
BACKGROUND AND PURPOSE: Alpha(1)-adrenoceptor antagonists are extensively used in the treatment of hypertension and lower urinary tract symptoms associated with benign prostatic hyperplasia. Among the side effects, ejaculatory dysfunction occurs more frequently with drugs that are relatively selective for alpha(1A)-adrenoceptors compared with other drugs of this class. This suggests that alpha(1A)-adrenoceptors may contribute to ejaculation. However, this has not been studied at the molecular level.
EXPERIMENTAL APPROACH: The physiological contribution of each alpha(1)-adrenoceptor subtype was characterized using alpha(1)-adrenoceptor subtype-selective knockout (KO) mice (alpha(1A)-, alpha(1B)- and alpha(1D)-AR KO mice) since the subtype-specific drugs available are only moderately selective. We analysed the role of alpha(1)-adrenoceptors in the blood pressure and vascular response as well as ejaculation by determining these variables in alpha(1)-adrenoceptor subtype-selective KO mice and in mice with all their alpha(1)-adrenoceptor subtypes deleted (alpha(1)-AR triple-KO mice).
KEY RESULTS: The pregnancy rate was reduced by 50% in alpha(1A)-adrenoceptor KO mice, and this reduction was dramatically enhanced in alpha(1)-adrenoceptor triple-KO mice. Contractile tension of the vas deferens in response to noradrenaline was markedly decreased in alpha(1A)-adrenoceptor KO mice, and this contraction was completely abolished in alpha(1)-adrenoceptor triple-KO mice. This attenuation of contractility was also observed in the electrically stimulated vas deferens.
CONCLUSIONS AND IMPLICATIONS: These results demonstrate that alpha(1)-adrenoceptors, particularly alpha(1A)-adrenoceptors, are required for normal contractility of the vas deferens and consequent sperm ejaculation as well as having a function in fertility.
A Sanbe; Y Tanaka; Y Fujiwara; H Tsumura; J Yamauchi; S Cotecchia; K Koike; G Tsujimoto; A Tanoue
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-07-02
Journal Detail:
Title:  British journal of pharmacology     Volume:  152     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-10-01     Completed Date:  2008-01-16     Revised Date:  2013-06-06    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  332-40     Citation Subset:  IM    
Department of Pharmacology, National Research Institute for Child Health and Development, Setagaya-ku, Tokyo, Japan.
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MeSH Terms
Adrenergic alpha-Antagonists / adverse effects
Blood Pressure / physiology
Ejaculation / drug effects,  physiology*
Electric Stimulation
Fertility / physiology
Mice, Inbred C57BL
Mice, Knockout
Muscle Contraction / physiology
Receptors, Adrenergic, alpha-1 / genetics,  metabolism*
Semen / physiology
Vas Deferens / physiology
Reg. No./Substance:
0/Adra1a protein, mouse; 0/Adra1b protein, mouse; 0/Adra1d protein, mouse; 0/Adrenergic alpha-Antagonists; 0/Receptors, Adrenergic, alpha-1
Comment In:
Br J Pharmacol. 2007 Oct;152(3):289-90   [PMID:  17603543 ]

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