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.
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology*; D002794:Choline / Q000378:metabolism; D005260:Female; D005704:Gallbladder / Q000378:metabolism*; D006168:Guinea Pigs; D006584:Hexamethonium Compounds / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000502:physiology*; D011963:Receptors, GABA-A; D017981:Receptors, Neurotransmitter / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D006584:Hexamethonium Compounds; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D017981:Receptors, Neurotransmitter; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D001418:Baclofen; D002794:Choline; D000109:Acetylcholine; D001640:Bicuculline