Article date: September 2017
By: Takahiro Shimizu, Shogo Shimizu, Naoki Wada, Shun Takai, Nobutaka Shimizu, Youichirou Higashi, Katsumi Kadekawa, Tsuyoshi Majima, Motoaki Saito, Naoki Yoshimura in Volume 174, Issue 18, pages 3072-3080
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.
DOI: 10.1111/bph.13941
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