Centrally administered prostaglandin E2 suppresses the micturition reflex in rats

Abstract

Prostaglandin E₂ (PGE₂) facilitates the micturition reflex at the lower urinary tract and spinal cord levels. However, the roles of brain PGE₂ in reflex regulation remain unclear. Therefore, we aimed to investigate the effects of intracerebroventricularly administered PGE₂ on the micturition reflex. We further investigated whether the PGE₂-induced responses were dependent on the sympathetic nervous system (SNS) and identified the brain E-prostanoid receptor subtypes (EP₁–EP₄) involved in PGE₂-induced effects. Intracerebroventricularly administered PGE₂ (0.1, 0.3, or 1 nmol/rat) dose-dependently increased the intercontraction intervals (ICI) and threshold pressure required to induce micturition (TP) without altering maximal voiding pressure in urethane-anesthetized (0.8 g/kg, ip) male rats. PGE₂ (1 nmol/rat) significantly increased the mean blood pressure; 6-hydroxydopamine-induced chemical sympathectomy ameliorated this increase. In contrast, chemical sympathectomy had no significant effect on the PGE₂-induced increases in ICI and TP. Intracerebroventricularly pretreated SC51322 (EP₁ receptor antagonist, 100 nmol/rat) and PF04418948 (EP₂ receptor antagonist, 100 nmol/rat), but not L-798106 (EP₃ receptor antagonist, 100 nmol/rat) or L-161982 (EP₄ receptor antagonist, 100 nmol/rat), significantly attenuated the PGE₂ (1 nmol/rat)-induced changes in ICI and TP. These results suggest that centrally administered PGE₂ suppresses the rat micturition reflex through brain EP₁ and EP₂ receptors, independent of SNS activation.