Neuroeffector mechanisms in the voiding cycle of the guinea-pig urinary bladder

1. The effect of drugs expected to modify cholinergic (atropine, physostigmine) or GABA-ergic (GABA, picrotoxin, bicuculline methiodide, BMI) neurotransmission were investigated on the voiding cycle of the urinary bladder in urethane-anaesthetized guinea-pigs. 2. Transvesical saline infusion elicited a series of regular voiding cycles which were abolished by topical tetrodotoxin as well as by topical or intravenous (i.v.) hexamethonium, thus indicating their reflex neurogenic origin. 3. Either i.v. or topical atropine decreased amplitude and duration of micturition contraction, reduced efficiency of bladder voiding and, in about 30% of preparations, suppressed micturition (overflow incontinence). Either topical or i.v. physostigmine potentiated, in an atropine-sensitive manner, voiding efficiency. 4. GABA was administered during the ascending limb of the voiding cycle: i.v. GABA inhibited while topical GABA increased efficiency of the first voiding cycle. Both direction and intensity of the effect of GABA were dependent upon initial pressures. The second and following voiding cycles after GABA administration were inhibited transiently. 5. Either topical or i.v. picrotoxin or BMI potentiated the efficiency of the voiding cycle of the guinea-pig bladder. In these preparations either i.v. or topical GABA (administered during the ascending limb of the voiding cycle) produced only inhibitory effects on voiding efficiency. 6. These findings indicate that, in guinea-pigs, bladder voiding is largely dependent upon an intact cholinergic neurotransmission. Although amplitude of the initial voiding contraction is largely atropine-resistant, its duration and, consequently, degree of bladder voiding, are strongly influenced by blockade (atropine) or potentiation (physostigmine) of cholinergic neurotransmission. Endogenous GABA-ergic mechanism modulate, possibly at peripheral level, the voiding efficiency of the guinea-pig bladder. GABA exerts a complex neuromodulatory influence on voiding function, its overall effect being mainly influenced by resting parameters.