title: A Stress-Related Peptide Bombesin Centrally Induces Frequent Urination through Brain Bombesin Receptor Types 1 and 2 in the Rat.
abstract: Stress exacerbates symptoms of bladder dysfunction including overactive bladder and bladder pain syndrome, but the underlying mechanisms are unknown. Bombesin-like peptides and bombesin receptor types 1 and 2 (BB1 and BB2, respectively) in the brain have been implicated in the mediation/integration of stress responses. In this study, we examined effects of centrally administered bombesin on micturition, focusing on their dependence on 1) the sympathoadrenomedullary system (a representative mechanism activated by stress exposure) and 2) brain BB receptors in urethane-anesthetized (1.0-1.2 g/kg, i.p.) male rats. Intracerebroventricularly administered bombesin significantly shortened intercontraction intervals (ICI) at both doses (0.1 and 1 nmol/animal) without affecting maximal voiding pressure. Bombesin at 1 nmol induced significant increments of plasma noradrenaline and adrenaline levels, which were both abolished by acute bilateral adrenalectomy. On the other hand, adrenalectomy showed no effects on the bombesin-induced shortening of ICI. Much lower doses of bombesin (0.01 and 0.03 nmol/animal, i.c.v.) dose-dependently shortened ICI. Pretreatment with either a BB1 receptor antagonist (BIM-23127; d-Nal-cyclo[Cys-Tyr-d-Trp-Orn-Val-Cys]-Nal-NH2; 3 nmol/animal, i.c.v.) or a BB2 receptor antagonist (BEA; H-d-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-NHEt; 3 nmol/animal, i.c.v.), respectively, suppressed the BB (0.03 nmol/animal, i.c.v.)-induced shortening of ICI, whereas each antagonist by itself (1 and 3 nmol/animal, i.c.v.) had no significant effects on ICI. Bombesin (0.03 nmol/animal, i.c.v.) significantly reduced voided volume per micturition and bladder capacity without affecting postvoid residual volume or voiding efficiency. These results suggest that brain bombesin and BB receptors are involved in facilitation of the rat micturition reflex to induce bladder overactivity, which is independent of the sympathoadrenomedullary outflow modulation.
authors.affiliation: Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan (T.S., S.S., Y.H., K.N., M.S.); and Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania (T.S., N.Y.) shimizu@kochi-u.ac.jp.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan (T.S., S.S., Y.H., K.N., M.S.); and Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania (T.S., N.Y.).
authors.forename: Shogo
authors.initials: S
authors.lastname: Shimizu
authors.affiliation: Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan (T.S., S.S., Y.H., K.N., M.S.); and Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania (T.S., N.Y.).
authors.forename: Youichirou
authors.initials: Y
authors.lastname: Higashi
authors.affiliation: Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan (T.S., S.S., Y.H., K.N., M.S.); and Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania (T.S., N.Y.).
authors.forename: Kumiko
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan (T.S., S.S., Y.H., K.N., M.S.); and Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania (T.S., N.Y.).
authors.forename: Naoki
authors.initials: N
authors.lastname: Yoshimura
authors.affiliation: Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan (T.S., S.S., Y.H., K.N., M.S.); and Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania (T.S., N.Y.).
authors.forename: Motoaki
authors.initials: M
authors.lastname: Saito
mesh_terms: D000818:Animals; D001839:Bombesin / Q000008:administration & dosage*; D001921:Brain / Q000187:drug effects* / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D018004:Receptors, Bombesin / Q000819:agonists / Q000502:physiology*; D014554:Urination / Q000187:drug effects* / Q000502:physiology*
chemical_list: D018004:Receptors, Bombesin; D001839:Bombesin