Alfaxalone, pentobarbital and diazepam potentiate gamma-aminobutyric acid-induced depolarizations in single myenteric neurons of guinea pig intestine.
Intracellular electrophysiological recordings were made from myenteric neurons of guinea pig ileum maintained in vitro. gamma-Aminobutyric acid (GABA), applied by superfusion (1-300 microM) or by pressure ejection from a fine-tipped pipette positioned near the impaled neuron, depolarized some neurons. GABA-induced depolarizations were mimicked by muscimol (1-100 microM) applied by superfusion and were blocked by bicuculline (30 microM) and picrotoxin (60 microM). The estimated reversal potential for the GABA-induced depolarization was -18 +/- 3 mV when recordings were made with potassium chloride (2 M)-filled microelectrodes. These results indicate that GABA was acting at GABAA receptors on myenteric neurons. GABAA-mediated depolarizations (GABA applied by pressure ejection) were potentiated by the steroid anesthetic, alfaxalone (0.5 microM) (51 +/- 15%, n = 6), by pentobarbital (60 microM) (29 +/- 4%, n = 7) and diazepam (0.3 microM) (41 +/- 14%, n = 7). Alfaxalone (greater than 1 microM) and pentobarbital (greater than 100 microM) mimicked the GABA-induced depolarization. Cortisol (30-1000 pM) did not alter the amplitude of GABA responses when GABA was applied by pressure ejection (n = 6) or by superfusion (n = 6). These data indicate that GABAA receptors on myenteric neurons contain binding sites for some steroids, barbiturates and benzodiazepines and that responses mediated at enteric GABAA receptors can be modified by drugs acting at these allosteric binding sites.
Bertrand
P P
PP
Department of Pharmacology and Toxicology, Michigan State University, East Lansing.
Galligan
J J
JJ
D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D003975:Diazepam / Q000494:pharmacology*; D004357:Drug Synergism; D006168:Guinea Pigs; D006854:Hydrocortisone / Q000494:pharmacology; D007422:Intestines / Q000294:innervation*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009118:Muscimol / Q000494:pharmacology; D010424:Pentobarbital / Q000494:pharmacology*; D011277:Pregnanediones / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D000777:Anesthetics; D011277:Pregnanediones; D011963:Receptors, GABA-A; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; C006477:alphaxalone; D010424:Pentobarbital; D003975:Diazepam; D006854:Hydrocortisone