5-Hydroxytryptamine-induced bladder hyperactivity via the 5-HT2A receptor in partial bladder outlet obstruction in rats.
We investigated the effects of partial bladder outlet obstruction (BOO) on the function and gene expression of 5-hydroxytryptamine (5-HT) receptor subtypes in rat bladder. Isometric contractions of the isolated bladders from sham-operated control and BOO rats were examined. The contractile responses to 5-HT were significantly increased in BOO rat bladder strips, while the responses to KCl, carbachol, or phenylephrine were not different from the control. The 5-HT-induced hypercontraction in BOO rat bladder strips was inhibited by ketanserin, a 5-HT(2A) receptor antagonist. The contractile responses to 5-HT in bladder strips were not affected by urothelium removal from the intact bladder. The gene expression of 5-HT receptor subtypes in the bladders was analyzed by RT-PCR. The mRNA expression of the 5-HT(2A), 5-HT(2B), 5-HT(2C), 5-HT(4), and 5-HT(7) receptors was detected in both the control and BOO rat bladders. Quantitative RT-PCR analysis showed there was a significant increase of 5-HT(2A) receptor mRNA in the BOO rat bladder compared with the control bladder. On the other hand, the gene expression of the 5-HT(4) receptor was not changed in the BOO rat bladder. These results suggest that the increased contractile responses to 5-HT in BOO rat bladder may be partly caused by 5-HT(2A) receptor upregulation in the detrusor smooth muscles.
Laboratory for Development Pharmacology, Pharmaceuticals Research Center, Asahi Kasei Pharma Corporation, Izunokuni-shi, Shizuoka, Japan.
Takumi
T
Sakai
Ken-ichi
K
Kasahara
Ken-ichi
K
Tomita
Ichiro
I
Ikegaki
Hiroshi
H
Kuriyama
D000818:Animals; D005260:Female; D007650:Ketanserin / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D044402:Receptor, Serotonin, 5-HT2A / Q000096:biosynthesis / Q000502:physiology*; D011985:Receptors, Serotonin / Q000096:biosynthesis; D012701:Serotonin / Q000494:pharmacology; D001743:Urinary Bladder / Q000503:physiopathology*; D001748:Urinary Bladder Neck Obstruction / Q000503:physiopathology*; D053201:Urinary Bladder, Overactive / Q000503:physiopathology*
D012333:RNA, Messenger; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D012701:Serotonin; D007650:Ketanserin