Brain nicotinic acetylcholine receptors stimulation inhibits the micturition reflex in rats
Dr. Takahiro Shimizu (1), Yohei Shimizu (1), Hideaki Ono (1), Suo Zou (1), Dr. Masaki Yamamoto (1), Dr. Shogo Shimizu (1), Dr. Youichirou Higashi (1), Takaaki Aratake (1), Dr. Tomoya Hamada (1), Dr. Yoshiki Nagao (1), Prof. Motoaki Saito (1)
(1) Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Japan
Psychological stress exacerbates symptoms of bladder dysfunction. Previously, we reported that epibatidine (EP) [nicotinic acetylcholine receptor (nAChR) agonist] centrally activated a representative response to stress, the sympatho-adrenomedullary (SA) system, in rats1). In this study, we investigated effects of centrally administered EP on the micturition reflex and their dependence on the SA system in rats.
Urethane anesthetized (0.8 g/kg, ip) male Wistar rats (300-400 g) were used. Catheters were inserted into the bladder and the femoral artery to perform cystometrograms (CMG, 12 ml/h saline infusion) and to collect blood samples, respectively. Three hours after the surgery, EP (0.3 or 1 nmol/rat) or vehicle was icv administered. Plasma catecholamines (CA, noradrenaline and adrenaline) were measured at 5 min after the icv administration. In some rats, acute bilateral adrenalectomy (ADX) was performed before catheters insertion. When EP was intravenously administered, another catheter was inserted into the femoral vein. Effects of icv pretreated mecamylamine (MEC, 100 or 300 nmol/rat) (nAChR antagonist) on the EP-induced responses were also investigated.
(1) Centrally administered EP dose-dependently prolonged intercontraction intervals (ICI) and elevated plasma CA without affecting maximal voiding pressure (MVP) (Table 1). ADX almost abolished the EP-induced CA elevation without affecting the ICI prolongation. (2) Intravenously administered EP showed no significant effect on ICI. (3) MEC dose-dependently suppressed the EP-induced ICI prolongation and CA elevation.
Stimulation of brain nAChRs might inhibit the micturition reflex, independent of the SA outflow modulation.