Alpha1-adrenoceptors are required for normal male sexual function.
OBJECTIVE
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.


METHODS
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).


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
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.
Sanbe
A
A
Department of Pharmacology, National Research Institute for Child Health and Development, Setagaya-ku, Tokyo, Japan. asanbe@nch.go.jp
Tanaka
Y
Y
Fujiwara
Y
Y
Tsumura
H
H
Yamauchi
J
J
Cotecchia
S
S
Koike
K
K
Tsujimoto
G
G
Tanoue
A
A
D000317:Adrenergic alpha-Antagonists / Q000009:adverse effects; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D004542:Ejaculation / Q000187:drug effects / Q000502:physiology*; D004558:Electric Stimulation; D005260:Female; D005298:Fertility / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000502:physiology; D011247:Pregnancy; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics / Q000378:metabolism*; D012661:Semen / Q000502:physiology; D014649:Vas Deferens / Q000502:physiology
C547714:Adra1a protein, mouse; C547717:Adra1b protein, mouse; C547720:Adra1d protein, mouse; D000317:Adrenergic alpha-Antagonists; D018340:Receptors, Adrenergic, alpha-1