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

Brain serotoninergic nervous system is involved in bombesin-induced frequent urination through brain 5-HT7 receptors in rats.

Author information

1
Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan.
2
Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

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.

PMID:
28675470
PMCID:
PMC5573417
DOI:
10.1111/bph.13941
[Indexed for MEDLINE]
Free PMC Article

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