Does pharmacological activation of 5-HT1A receptors improve urine flow rate in female rats?

Am J Physiol Renal Physiol. 2016 Jul 1;311(1):F166-75. doi: 10.1152/ajprenal.00469.2015. Epub 2016 May 4.

Abstract

The role of 5-HT1A receptors in regulating voiding functions remains unclear, particularly regarding the urine flow rate (UFR) during voiding. This study examined the effects of 5-HT1A receptors on regulating urethral functions in female rats and investigated underlying modulatory mechanisms. Intravesical pressure (IVP), external urethral sphincter-electromyography (EUS-EMG), and UFR were simultaneously recorded during continuous transvesical infusion to examine the effects of a 5-HT1A receptor agonist (8-OH-DPAT) and antagonist (WAY-100635) on bladder and urethral functions. In addition, this study evaluated the independent roles of urethral striated and smooth muscles in the UFR in rats after a neuromuscular blockade (NMB) treatment and bilateral hypogastric nerve transection. Our results revealed that 8-OH-DPAT significantly increased the maximal UFR but reduced the mean UFR. This discrepancy may be because 8-OH-DPAT markedly increased the maximal UFR during the initial segment of the flow duration and subsequently induced an approximately zero level of long oscillatory waves during the remaining flow duration. Thus the mean UFR was reduced because of the prolonged approximately zero level of the UFR. However, paralyzing the EUS with an NMB agent, 8-OH-DPAT, significantly increased the maximal and mean UFRs because the prolonged zero level of the oscillatory UFR did not continue. These results support the hypothesis that the increased UFR in female rats during voiding is due to the induction of urethral smooth muscle relaxation by 8-OH-DPAT. This paper provides a detailed understanding of the role of 5-HT1A receptors in controlling the UFR in female rats.

Keywords: 8-OH-DPAT; EUS-EMG; WAY-100635; intravesical pressure; neuromuscular blockade.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Animals
  • Denervation
  • Electromyography
  • Female
  • Hypogastric Plexus / physiology
  • Neuromuscular Blocking Agents / pharmacology
  • Piperazines / pharmacology
  • Pyridines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Serotonin, 5-HT1A / drug effects*
  • Serotonin 5-HT1 Receptor Agonists / therapeutic use*
  • Serotonin 5-HT1 Receptor Antagonists / pharmacology
  • Serotonin Antagonists / pharmacology
  • Urethra / physiopathology
  • Urination / drug effects
  • Urodynamics / drug effects*

Substances

  • Neuromuscular Blocking Agents
  • Piperazines
  • Pyridines
  • Serotonin 5-HT1 Receptor Agonists
  • Serotonin 5-HT1 Receptor Antagonists
  • Serotonin Antagonists
  • Receptor, Serotonin, 5-HT1A
  • N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
  • 8-Hydroxy-2-(di-n-propylamino)tetralin