Brain hydrogen sulfide suppresses the micturition reflex via brain GABA receptors in rats

We recently reported that hydrogen sulfide (H₂S) is a possible relaxation factor in the rat bladder. However, there is no available information about the roles of central H₂S in the micturition reflex, so we investigated the effects of centrally administered GYY4137 (H₂S donor) and AOAA (H₂S synthesis inhibitor) on the micturition reflex in urethane-anesthetized (0.8 g/kg, ip) male Wistar rats. Cystometry was performed before and after the administration of GYY4137 (3 or 10 nmol/rat, icv) or AOAA (30 or 100 μg/rat, icv). In some rats, SR95531 (GABA_A receptor antagonist, 0.1 nmol/rat, icv) or SCH50911 (GABA_B receptor antagonist, 0.1 nmol/rat, icv) was administered 30 min before GYY4137 administration (10 nmol/rat, icv). Centrally administered GYY4137 dose-dependently prolonged the intercontraction intervals (ICI) without altering maximum voiding pressure (MVP). On the other hand, centrally administered AOAA dose-dependently shortened ICI without altering MVP. The AOAA (30 μg/rat, icv)-induced ICI shortening was reversed in the central presence of GYY4137 (10 nmol/rat, icv). Centrally pretreated SR95531 or SCH50911 significantly attenuated the GYY4137 (10 nmol/rat, icv)-induced prolongation of ICI, respectively. These findings suggest that endogenous brain H₂S can inhibit the rat micturition reflex via both GABA_A and GABA_B receptors in the brain.