Participation of GABA/benzodiazepine receptor system in the adrenal chromaffin cell function.
Histochemical studies have shown that GABA-containing nerve terminals impinge upon the chromaffin cells and that approximately 40% of the chromaffin cells store and release GABA. These observations are compatible with the possibility that GABA receptors located on specific populations of chromaffin cells can be activated either by GABA released from nerve terminals or by GABA released from adjacent chromaffin cells. Indeed, experiments with bicuculline indicate that in bovine chromaffin cells in culture and in the adrenal medulla of dog in vivo, the secretion of CA and opioid peptides mediated by activation of nicotinic receptors is under tonic control of GABA. In a series of pharmacological experiments in dog, we have shown that appropriate doses of GABA or other GABA-mimetic drugs release CA into the circulation. This release, comparable in its magnitude to that obtained by injecting a full pharmacological dose of carbamylcholine or by maximally efficient electrical stimulation of the splanchnic nerve, was not blocked by hexamethonium, naloxone or splanchnicotomy, but instead, was prevented by treatment with bicuculline methiodide. These data suggest that GABA-induced CA release is not the consequences of activation of transynaptic mechanisms involving either acetylcholine, enkephalin or GABA acting at the GABAB receptors, but rather the result of stimulation of GABAA receptors linked to C1- channels located on the membranes of the adrenal chromaffin cells. Because the administration of GABA was found to induce depolarization in autonomic mammalian ganglia in electrophysiological studies (DeGroat, 1970), we propose that the GABA-mediated release of CA from dog adrenal medulla is the consequence of chromaffin cell depolarization.(ABSTRACT TRUNCATED AT 250 WORDS)
D000612:4-Aminobutyrate Transaminase / Q000378:metabolism; D000313:Adrenal Medulla / Q000502:physiology*; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D004285:Dogs; D004744:Enkephalin, Methionine / Q000378:metabolism; D005968:Glutamate Decarboxylase / Q000378:metabolism; D009118:Muscimol / Q000494:pharmacology; D051381:Rats; D011963:Receptors, GABA-A / Q000502:physiology*; D012636:Secretory Rate / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D002395:Catecholamines; D011963:Receptors, GABA-A; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D004744:Enkephalin, Methionine; D000612:4-Aminobutyrate Transaminase; D005968:Glutamate Decarboxylase; D001418:Baclofen; D001640:Bicuculline