Brain serotoninergic nervous system is involved in bombesin-induced frequent urination through brain 5-HT 7 receptors in rats

Br J Pharmacol. 2017 Sep;174(18):3072-3080. doi: 10.1111/bph.13941. Epub 2017 Aug 3.

Abstract

Background and purpose: Psychological stress exacerbates symptoms of urinary bladder dysfunction; however, the underlying brain mechanisms are unclear. We have demonstrated that centrally administered bombesin, a stress-related neuropeptide, facilitates the rat micturition reflex. Brain bombesin-like peptides modulate the serotoninergic nervous system activity under stress conditions; therefore, we examined whether brain 5-HT is involved in the bombesin-induced increased frequency of urination in urethane-anaesthetised male Sprague-Dawley rats.

Experimental approach: Evaluation of intercontraction intervals (ICI) and maximal voiding pressure (MVP) during cystometrograms were started 1 h before i.c.v. administration of bombesin or i.c.v. pretreatment with the 5-HT receptor antagonists.

Key results: Bombesin (0.03 nmol per animal, i.c.v.) significantly reduced ICI without affecting MVP. The bombesin-induced response was significantly suppressed by acute depletion of brain 5-HT, which was induced by pretreatment with p-chlorophenylalanine, a 5-HT synthesis inhibitor. Bombesin at a lower dose (0.01 nmol per animal, i.c.v.) showed no significant effect on ICI, while it significantly reduced ICI in the presence of WAY-100635 (5-HT1A receptor antagonist, 0.1 or 0.3 μg per animal, i.c.v.), which can block the negative feedback control of 5-HT release. Bombesin (0.03 nmol per animal)-induced ICI reduction was significantly attenuated by SB269970 (5-HT7 receptor antagonist, 0.1 or 0.3 μg per animal, i.c.v.) but not by ritanserin (5-HT2 receptor antagonist, 0.3 or 1 μg per animal, i.c.v.).

Conclusions and implications: The brain serotoninergic nervous system is involved in the facilitation of the rat micturition reflex induced by bombesin-like peptides at least in part through brain 5-HT7 receptors.

MeSH terms

  • Animals
  • Autonomic Nervous System / drug effects*
  • Bombesin / administration & dosage
  • Bombesin / antagonists & inhibitors
  • Bombesin / pharmacology*
  • Brain / drug effects*
  • Brain / metabolism*
  • Dose-Response Relationship, Drug
  • Injections, Intraventricular
  • Male
  • Piperazines / pharmacology
  • Pyridines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Serotonin / metabolism*
  • Serotonin Receptor Agonists / administration & dosage
  • Serotonin Receptor Agonists / chemistry
  • Serotonin Receptor Agonists / pharmacology*
  • Structure-Activity Relationship
  • Urination / drug effects*

Substances

  • Piperazines
  • Pyridines
  • Receptors, Serotonin
  • Serotonin Receptor Agonists
  • serotonin 7 receptor
  • N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
  • Bombesin