Central and peripheral action of GABAA and GABAB agonists on small intestine motility in rats.
gamma-Aminobutyric acid (GABA) is known as a neurotransmitter in the central nervous system and in the enteric nervous system. The effects and the sites of action of GABA and of its GABAA (muscimol) and GABAB (baclofen) agonists were determined on intestinal motility of unanesthetized rats chronically fitted with intraparietal electrodes in the duodeno-jejunum and fasted for 8 h. GABA (6 mg/kg i.p.) induced a biphasic response i.e. a primary inhibition followed by a period of irregular spiking activity. Muscimol (4 mg/kg i.p.) inhibited the cyclic motor profile while baclofen (4 mg/kg i.p.) had a stimulatory effect chiefly at the duodenal level. Only baclofen intracerebroventricularly administered (1 microgram i.c.v.) was able to reproduce the intestinal motor effects observed after systemic injections. Bicuculline (a specific GABAA antagonist) blocked the inhibition induced by GABA and muscimol; atropine (i.p. and i.c.v.) antagonized the irregular spiking activity induced by GABA and baclofen. It is concluded that the dual effect of GABA can be explained by an action at 2 subtypes of receptors: GABAA and GABAB. Stimulation of GABAA receptors induced peripherally mediated inhibition of the duodeno-jejunal motility. On the contrary stimulation of the GABAB receptors increased and disrupted duodenal cyclic motility by a central action involving central and peripheral muscarinic receptors.
Fargeas
M J
MJ
Department of Pharmacology, INRA, Toulouse, France.
Fioramonti
J
J
Bueno
L
L
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001418:Baclofen / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D004576:Electromyography; D005769:Gastrointestinal Motility / Q000187:drug effects*; D007421:Intestine, Small / Q000187:drug effects / Q000294:innervation; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000502:physiology
D011963:Receptors, GABA-A; D009118:Muscimol; D009270:Naloxone; D001285:Atropine; D001418:Baclofen; D001640:Bicuculline; D010646:Phentolamine