5-Hydroxytryptamine-induced bladder hyperactivity via the 5-HT_2Areceptor in partial bladder outlet obstruction in rats

Abstract

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.

<b>Increased expression of 5-HT</b><b>_2A</b><b> and 5-HT</b><b>_2B</b><b> receptors in detrusor muscle after partial bladder outlet obstruction in </b><b>rats </b>

“…The contractile responses to 5-HT was significantly enhanced by pBOO, and expression of mRNA encoding the 5-HT 2A and 5-HT 2B receptors was increased in the detrusor muscle layer following pBOO. In rat bladder, multiple 5-HT receptor subtypes are expressed, including 5-HT 2A , 5-HT 2B , 5-HT 4 , and 5-HT 7 receptors; notably, the 5-HT 2 receptors are involved in 5-HTinduced contraction (25). In sham rats, expression of 5-HT 2A and 5-HT 2B receptor mRNA in the bladder smooth muscle cells was sparse ( Fig.…”

“…The procedure for this pBOO model was previously described (25). Rats were anesthetized by intraperitoneal injection of pentobarbital sodium (30-40 mg/kg).…”

“…5-HT induces smooth muscle contraction in the various tissues such as the intestine, artery, and urinary bladder (11,18). We previously showed that the 5-HT-induced bladder contractile response is enhanced approximately 2.8-fold and 5-HT 2A receptor mRNA is increased in the rat bladder on day 7 after pBOO (25). These changes might be related to detrusor overactivity secondary to pBOO.…”

“…One of the important functional changes in the bladder with pBOO is the contractile response associated with detrusor overactivity. Contractile responses to ATP and acetylcholine are changed by pBOO; however, descriptions of these changes are not consistent among reports (2,7,19,25). Therefore, the myogenic change caused by pBOO is not fully understood.…”

“…The procedure used for this test was described previously (25). Each bladder strip was mounted in a 10-mL organ bath containing 37°C Krebs-Henseleit solution aerated with a 95% O 2 -5% CO 2 gas mixture.…”