5-Hydroxytryptamine-induced bladder hyperactivity via the 5-HT2A receptor in partial bladder outlet obstruction in rats

Am J Physiol Renal Physiol. 2013 Apr 1;304(7):F1020-7. doi: 10.1152/ajprenal.00365.2012. Epub 2013 Jan 23.

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.

MeSH terms

  • Animals
  • Female
  • Ketanserin / pharmacology
  • Muscle Contraction / drug effects
  • RNA, Messenger / metabolism
  • Rats
  • Receptor, Serotonin, 5-HT2A / biosynthesis
  • Receptor, Serotonin, 5-HT2A / physiology*
  • Receptors, Serotonin / biosynthesis
  • Serotonin / pharmacology
  • Urinary Bladder / physiopathology*
  • Urinary Bladder Neck Obstruction / physiopathology*
  • Urinary Bladder, Overactive / physiopathology*

Substances

  • RNA, Messenger
  • Receptor, Serotonin, 5-HT2A
  • Receptors, Serotonin
  • Serotonin
  • Ketanserin