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

作者:Shimizu Takahiro; Shimizu Shogo; Wada Naoki; Takai Shun; Shimizu Nobutaka; Higashi Youichirou; Kadekawa Katsumi; Majima Tsuyoshi; Saito Motoaki; Yoshimura Naoki
来源:British Journal of Pharmacology, 2017, 174(18): 3072-3080.
DOI:10.1111/bph.13941

摘要

Background and PurposePsychological 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 ApproachEvaluation of intercontraction intervals (ICI) and maximal voiding pressure (MVP) during cystometrograms were started 1h before i.c.v. administration of bombesin or i.c.v. pretreatment with the 5-HT receptor antagonists. Key ResultsBombesin (0.03nmol 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 (0.01nmol 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 0.3g per animal, i.c.v.), which can block the negative feedback control of 5-HT release. Bombesin (0.03nmol per animal)-induced ICI reduction was significantly attenuated by SB269970 (5-HT7 receptor antagonist, 0.1 or 0.3g per animal, i.c.v.) but not by ritanserin (5-HT2 receptor antagonist, 0.3 or 1g per animal, i.c.v.). Conclusions and ImplicationsThe 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.

  • 出版日期2017-9