Effect of gamma-aminobutyric acidA receptor agonists and antagonists on the release of enkephalin-containing peptides from dog adrenal gland.
Chromaffin cells of the adrenal medulla are known to store and release catecholamines, Met5-enkephalin (ME)-like peptides and gamma-aminobutyric acid (GABA). The present study documents that stimulation of GABAA receptors located on chromaffin cell membranes of canine adrenal glands, eliciting depolarization of chromaffin cell membranes, modulates the responsiveness of chromaffin cells to splanchnic nerve stimulation. 4,5,6,7-Tetrahydroisoxazolo[5,4-c]pyridin-3-ol (0.143 mmol/2 ml/min), a selective GABAA receptor agonist infused into the aortic pouch, increases the release of ME-like peptides and catecholamines into the adrenal effluent blood. Prior infusion into the aortic pouch of the GABAA receptor blocker, bicuculline (0.05 mmol/2 ml/min), prevents the 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol-elicited release of both substances. A stoichiometric relationship exists between the release of both substances; 1 nmol/ml of plasma of catecholamines was coreleased with 2 pmol/ml of plasma of ME-like peptides. The chromatographic profile on a Sephadex G-75 column indicates that, after injection of 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol, various MW forms of ME-like peptides are released into the adrenal effluent blood. A similar profile for the release of ME-like peptides was obtained when electrical stimulation (10 V/6 Hz) of the splanchnic nerve was used as a stimulus. These data suggest that direct stimulation of GABAA receptors causes depolarization of chromaffin cell membranes by a burst of Cl- channel opening and triggers neurotransmitter release.(ABSTRACT TRUNCATED AT 250 WORDS)
Fujimoto
M
M
Laboratory of Preclinical Pharmacology, National Institute of Mental Health, Saint Elizabeths Hospital, Washington, D.C.
Kataoka
Y
Y
Guidotti
A
A
Hanbauer
I
I
D000313:Adrenal Medulla / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism; D004285:Dogs; D004558:Electric Stimulation; D004745:Enkephalins / Q000378:metabolism*; D005260:Female; D007555:Isoxazoles / Q000494:pharmacology*; D010080:Oxazoles / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000502:physiology*; D013153:Splanchnic Nerves / Q000502:physiology
D000700:Analgesics; D002395:Catecholamines; D004745:Enkephalins; D007555:Isoxazoles; D010080:Oxazoles; D011963:Receptors, GABA-A; C015542:gaboxadol; D001640:Bicuculline