3H-ACh release from guinea pig gallbladder evoked by GABA through the bicuculline-sensitive GABA receptor.

We investigated the effect of GABA on the spontaneous efflux of 3H-acetylcholine (ACh) from the isolated guinea pig gallbladder loaded with 3H-choline. Application of GABA (10(-5) M) caused a significant increase in the fractional rate of tritium efflux. This GABA-evoked efflux of ACh was inhibited by the perfusion of tetrodotoxin (10(-6) M) and Ca-free medium. Nipecotic acid (10(-4) M) did not affect the GABA-evoked release of ACh, indicating that ACh was not released by the entry of GABA into cholinergic nerve terminals. Bicuculline (10(-6) M) and furosemide (10(-6) M), the chloride ion channel blocker, inhibited the GABA-evoked ACh release. The application of muscimol (10(-5) M), but not baclofen (10(-5) M) also produced an increase in the fractional rate of ACh release. Thus, the GABA receptors involved in the increase of ACh release are bicuculline-sensitive. The GABA-evoked release of ACh was not altered by the perfusion with hexamethonium (10(-5) M), thus indicating the presence of GABA receptors on the postganglionic cholinergic neurons. These findings suggest that bicuculline-sensitive GABA receptors probably coupled to a Cl- ionophore are present on postganglionic cholinergic neurons and are involved in the increase of ACh release in guinea pig gallbladder.