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

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.

Psychological/mental stress‐induced effects on urinary function: Possible brain molecules related to psychological/mental stress‐induced effects on urinary function

“…In our study, PCPA‐induced acute depletion of brain serotonin suppressed the centrally administered BB‐induced ICI shortening (Fig. 2), and the BB‐induced response was attenuated by central pretreatment with SB269970 (5‐HT 7 receptor antagonist), showing that brain BB‐like peptides might be involved in the facilitation of micturition in rats through the brain serotoninergic nervous system/5‐HT 7 receptors 102 …”

“…2), and the BB-induced response was attenuated by central pretreatment with SB269970 (5-HT 7 receptor antagonist), showing that brain BB-like peptides might be involved in the facilitation of micturition in rats through the brain serotoninergic nervous system/5-HT 7 receptors. 102…”

“…* P < 0.05 versus values before BB (−10 to 0 min). Reproduced from Shimizu et al 102 . with permission from John Wiley and Sons.…”

Angiotensin II, a stress‐related neuropeptide in the CNS, facilitates micturition reflex in rats

“…Data subjected to statistical analysis were from a group size of at least five. Additionally, the group size was determined according to the expected difference in a desired endpoint measurement from our preliminary experiment and the mean of the SDs reported in our previous reports (Kawamoto et al ., ; Shimizu et al ., ). Eight rats were excluded due to cannula misplacement as described above.…”

Brain nitric oxide induces facilitation of the micturition reflex through brain glutamatergic receptors in rats

“…Cystometric studies were performed according to the methods previously reported. 19,22,23 Briefly, after the surgery described above, the bladder catheter was connected to a pressure transducer (DX-100; Nihon Koden, Tokyo, Japan) for measurements of intravesical pressure and to a syringe pump for intravesical instillation of sterile saline at a rate of 12 mL/h. Intravesical pressure was recorded using a PowerLab System (AD Instruments, Bella Vista, Australia).…”