ENTERIC GABA-CONTAINING NERVES PROJECTING TO THE GUINEA-PIG INFERIOR MESENTERIC GANGLION MODULATE ACETYLCHOLINE-RELEASE

1. The effect of GABA and GABA receptor-modulating drugs on release of [H-1]acetylcholine was studied in the guinea-pig inferior mesenteric ganglion. 2. GABA caused a dose-dependent increase in [H-3]acetylcholi ne release during stimulation of the lumbar colonic nerves. Muscimol ( 10 muM) and diazepam (5 muM) also increased [H-3]acetylcholine release during stimulation of the lumbar colonic nerves whereas baclofen (10 muM) had no effect. 3. Bicuculline (20-100 muM) and picrotoxin (50 muM ) alone reduced [H-3]acetylcholine release during electrical stimulati on of the lumbar colonic nerves whereas phaclofen (300 muM) had no eff ect. 4. Bicuculline (100 muM) significantly decreased whereas diazepam (5 muM) significantly increased distension-induced [H-3]acetylcholine release. 5. Colonic distension significantly increased [H-3]GABA rele ase in the inferior mesenteric ganglion compared to basal periods when the colon was not distended. Distension-induced release of [H-3]GABA resulted from active neuronal transmission from the colon to the infer ior mesenteric ganglion, since perfusion of the inferior mesenteric ga nglion with tetrodoxin (1 muM) reduced basal release of [H-3]GABA and abolished distension-evoked increases in the release of [H-3]GABA. 6. In contrast to its excitatory effects on peripheral colonic afferent c holinergic nerves, exogenous GABA caused a dose-dependent decrease in [H-3]acetylcholine release during electrical stimulation of the centra l lumbar splanchnic nerves. Baclofen (10 muM) also inhibited [3 H]acet ylcholine release whereas muscimol (10 muM) or diazepam (5 muM) had no effect. Phaclofen (300 muM) antagonized the inhibitory effects of exo genous GABA (10 muM) and of baclofen (10 muM). Bicuculline (100 muM), picrotoxin (50 mum) and phaclofen (300 muM) alone had no effect on [H- 3]acetylcholine release during splanchnic nerve stimulation. 7. Phaclo fen (300 muM) increased [H-3]acetylcholine release during simultaneous electrical stimulation of the lumbar colonic nerves and splanchnic ne rves and when GABA(A) receptors were blocked by bicuculline (20 muM). 8. The data suggest that GABA(A) receptors facilitate release of acety lcholine from peripheral cholinergic mechanosensory nerves projecting from the colon to the inferior mesenteric ganglion and that GABA(B) re ceptors inhibit release of acetylcholine from central cholinergic nerv es. Enteric GABA-containing nerves projecting to the inferior mesenter ic ganglion are mechanosensory. Endogenous release of GABA may act on GABA(A) receptors to facilitate peripheral cholinergic mechanosensory transmission and/or on GABA(B) receptors to inhibit central cholinergi c transmission.