Short- and long-term effects of silodosin, a selective alpha 1A-adrenoceptor antagonist, on ejaculatory function in rats.
OBJECTIVE
To investigate the short- and long-term effects of silodosin, a selective alpha(1A)-adrenoceptor antagonist, on spontaneous seminal emission by isolated rats and on the properties of alpha(1)-adrenoceptor subtypes in the rat seminal vesicle, as silodosin produces a relatively high incidence rate of abnormal ejaculation and chronic administration of receptor antagonists causes an up-regulation in the targeted receptor.


METHODS
Rats were treated with two doses (0.1 and 3 mg/kg/day) of silodosin orally for 3 or 30 days. Spontaneous seminal emission was studied during the 3-day observation period before completing treatment. The expression levels of alpha(1A), alpha(1B) and alpha(1D)-adrenoceptor mRNAs in the rat seminal vesicle and prostate were quantified by real-time reverse transcription-polymerase chain reaction using SYBR Green I.


RESULTS
The administration of two doses of silodosin for 3 or 30 days caused a significant dose-dependent reduction in the number of ejaculatory plugs and in their dry weight. However, in rats receiving the low dose of silodosin the inhibitory effect of the drug on spontaneous seminal emission diminished significantly with chronic usage over time. Although short-term administration of silodosin did not affect expression levels of any alpha(1)-adrenoceptor subtype mRNAs in the rat seminal vesicle and prostate, long-term administration of silodosin caused a significant up-regulation in the mRNA expression of alpha(1A)-adrenoceptor in a tissue-dependent manner.


CONCLUSIONS
Silodosin-induced up-regulation of alpha(1A)-adrenoceptor mRNA in the rat seminal vesicle might indicate potential differences in the inhibitory effect of this drug on ejaculatory function with chronic usage over time.
Yono
Makoto
M
Department of Urology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. yonomakoto@hotmail.com
Yamamoto
Yasuhiro
Y
Imanishi
Aya
A
Fukagawa
Atsushi
A
Latifpour
Jamshid
J
Yoshida
Masaki
M
D000199:Actins / Q000378:metabolism; D058668:Adrenergic alpha-1 Receptor Antagonists; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004542:Ejaculation / Q000187:drug effects*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1; D012669:Seminal Vesicles / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D000199:Actins; C547715:Adra1a protein, rat; D058668:Adrenergic alpha-1 Receptor Antagonists; D007211:Indoles; D012333:RNA, Messenger; D018340:Receptors, Adrenergic, alpha-1; C095285:silodosin; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases