Faculty Collaboration Database

Enteric GABA-containing nerves projecting to the guinea-pig inferior mesenteric ganglion modulate acetylcholine release. J Physiol 1993 Nov;471:191-207

Date

11/01/1993

Pubmed ID

8120803

Pubmed Central ID

PMC1143958

DOI

10.1113/jphysiol.1993.sp019897

Scopus ID

2-s2.0-0027436451 (requires institutional sign-in at Scopus site)   18 Citations

Abstract

1. The effect of GABA and GABA receptor-modulating drugs on release of [3H]acetylcholine was studied in the guinea-pig inferior mesenteric ganglion. 2. GABA caused a dose-dependent increase in [3H]acetylcholine release during stimulation of the lumbar colonic nerves. Muscimol (10 microM) and diazepam (5 microM) also increased [3H]acetylcholine release during stimulation of the lumbar colonic nerves whereas baclofen (10 microM) had no effect. 3. Bicuculline (20-100 microM) and picrotoxin (50 microM) alone reduced [3H]acetylcholine release during electrical stimulation of the lumbar colonic nerves whereas phaclofen (300 microM) had no effect. 4. Bicuculline (100 microM) significantly decreased whereas diazepam (5 microM) significantly increased distension-induced [3H]acetylcholine release. 5. Colonic distension significantly increased [3H]GABA release in the inferior mesenteric ganglion compared to basal periods when the colon was not distended. Distension-induced release of [3H]GABA resulted from active neuronal transmission from the colon to the inferior mesenteric ganglion, since perfusion of the inferior mesenteric ganglion with tetrodotoxin (1 microM) reduced basal release of [3H]GABA and abolished distension-evoked increases in the release of [3H]GABA. 6. In contrast to its excitatory effects on peripheral colonic afferent cholinergic nerves, exogenous GABA caused a dose-dependent decrease in [3H]acetylcholine release during electrical stimulation of the central lumbar splanchnic nerves. Baclofen (10 microM) also inhibited [3H]acetylcholine release whereas muscimol (10 microM) or diazepam (5 microM) had no effect. Phaclofen (300 microM) antagonized the inhibitory effects of exogenous GABA (10 microM) and of baclofen (10 microM). Bicuculline (100 microM), picrotoxin (50 microM) and phaclofen (300 microM) alone had no effect on [3H]acetylcholine release during splanchnic nerve stimulation. 7. Phaclofen (300 microM) increased [3H]acetylcholine release during simultaneous electrical stimulation of the lumbar colonic nerves and splanchnic nerves and when GABAA receptors were blocked by bicuculline (20 microM). 8. The data suggest that GABAA receptors facilitate release of acetylcholine from peripheral cholinergic mechanosensory nerves projecting from the colon to the inferior mesenteric ganglion and that GABAB receptors inhibit release of acetylcholine from central cholinergic nerves. Enteric GABA-containing nerves projecting to the inferior mesenteric ganglion are mechanosensory. Endogenous release of GABA may act on GABAA receptors to facilitate peripheral cholinergic mechanosensory transmission and/or on GABAB receptors to inhibit central cholinergic transmission.

Author List

Parkman HP, Stapelfeldt WH, Williams CL, Lennon VA, Szurszewski JH

Author

Carol L. Williams PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acetylcholine
Animals
Baclofen
Bicuculline
Colon
Diazepam
Electric Stimulation
Ganglia, Sympathetic
Guinea Pigs
In Vitro Techniques
Male
Mesentery
Muscimol
Neural Pathways
Receptors, GABA-A
Receptors, GABA-B
Splanchnic Nerves
Synaptic Transmission
gamma-Aminobutyric Acid