Abstract

1. The effects of GABA on release of acetylcholine and on contractility of the smooth muscle were studied in the myenteric plexus-longitudinal muscle preparation of the guinea pig. Acetylcholine was determined as radiolabelled transmitter from strips preloaded with 3H-choline. 2. GABA (1 - 300 microM) caused an increase in resting tension of smooth muscle as well as an increase in release of acetylcholine that was considerably reduced by tetrodotoxin. The facilitation by GABA of acetylcholine release exhibited a marked tachyphylaxis. The increase in muscle tension was clearly related to the increase in acetylcholine release. Muscimol (0.1 - 10 microM) also enhanced the release of acetylcholine. The effects of GABA on acetylcholine release and on longitudinal muscle contraction were competitively antagonized by bicuculline and picrotoxin. 3. GABA (1 - 300 microM) inhibited both release of acetylcholine and contractions evoked by electrical stimulation. Muscimol (1, 10 microM) did not modify the evoked release. The inhibitory effects of GABA were not antagonized by bicuculline or picrotoxin. 4. It is suggested that GABA facilitates and inhibits acetylcholine release, and in turn intestinal motility via two receptors with different pharmacological properties.

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