Galanin inhibition of enteric cholinergic neurotransmission: guanosine triphosphate-binding protein interactions with adenylate cyclase.
BACKGROUND
The ability of galanin, a unique 29 amino acid peptide, to affect cholinergic neurotransmission was examined in the guinea pig myenteric plexus.


METHODS
The effects of galanin on tritiated acetylcholine ([3H]ACh) release were studied with cultured guinea pig myenteric plexus neurons. Functional correlations were made with longitudinal strips of ileal smooth muscle with attached myenteric plexus for examination of isometric contraction.


RESULTS
Galanin abolished potassium-stimulated [3H]ACh release (170% +/- 18% of basal vs 109% +/- 16%). Galanin inhibited [3H]ACh release stimulated by forskolin or cholera toxin. [3H]ACh release stimulated by cholecystokin octapeptide, calcitonin gene-related peptide, substance P, or vasoactive intestinal peptide was also suppressed by galanin (10(-8) mol/L). Inhibitory effects were reversed by pertussis toxin preexposure, indicating involvement of guanosine triphosphate-binding proteins. Galanin inhibited contractility of longitudinal smooth muscle strips exposed to cholecystokinin-8 (EC50 7.0 X 10(-9) mol/L for cholecystokinin alone vs 1.3 X 10(-8) mol/L for cholecystokinin-8 plus galanin) and abolished contractile responses to calcitonin gene-related peptide.


CONCLUSIONS
Galanin inhibits cholinergic neurotransmission in myenteric plexus neurons. Inhibitory effects involve guanosine triphosphate-binding protein mediation.
Mulholland
M W
MW
Department of Surgery, University of Michigan, Ann Arbor 48109-0331.
Schoeneich
S
S
Flowe
K
K
D000109:Acetylcholine / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D004347:Drug Interactions; D019204:GTP-Binding Proteins / Q000378:metabolism*; D019004:Galanin; D006168:Guinea Pigs; D007422:Intestines / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009197:Myenteric Plexus / Q000187:drug effects*; D009433:Neural Inhibition; D009479:Neuropeptides / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology*; D013268:Stimulation, Chemical
D009479:Neuropeptides; D010455:Peptides; D019004:Galanin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D000109:Acetylcholine