GABAA- and GABAB-receptor-mediated modification of intestinal motility.
The actions of gamma-aminobutyric acid (GABA) and its analogues, 3-amino-1-propanesulphonic acid (3APS) and baclofen, have been investigated using isolated segments of the guinea-pig ileum and distal colon. GABA and 3APS, but not baclofen, induced GABAA-receptor mediated effects; prompt, dose-dependent contractions of the ileum which were antagonised by bicuculline, picrotoxinin, piretanide, tetramethylenedisulphotetramine, atropine and tetrodotoxin. Baclofen and GABA, but not 3APS, induced a dose-dependent GABAB-receptor mediated depression of electrically elicited twitch contractions of the ileum, unaffected by the GABAA-receptor antagonists or by antagonism of adenosine, adrenergic, opiate or nicotinic receptors. In the distal colon, baclofen and GABA caused a bicuculline- and picrotoxinin-insensitive depression of spontaneous cholinergic contractions. Desensitization to GABA and baclofen, and cross-desensitization to both agonists was observed. Combined antagonism of GABAA-receptors and desensitization to baclofen slowed pellet expulsion to the same extent as GABA desensitization alone, indicating that both GABAA- and GABAB-receptor sites are involved in this modification of peristalsis by GABA.
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D003106:Colon / Q000187:drug effects; D005260:Female; D018756:GABA Antagonists; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000187:drug effects*; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives
D018756:GABA Antagonists; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D001418:Baclofen