Intrinsic gamma aminobutyric acid receptors modulate the release of catecholamine from canine adrenal gland in situ.
Immunohistochemical analysis documented the presence of gamma-aminobutyric acid (GABA)-containing fibers and GABA-containing chromaffin cells in canine adrenal glands. A dense network of fibers was visualized at the boundary between medullary and cortical cells, and, in the medullary tissue, GABA-containing fibers surrounded chromaffin cells. Some of these fibers enter the adrenal medulla together with splanchnic cholinergic nerves. The functional role of the GABAergic system in the regulation of catecholamine release from adrenal chromaffin cells was studied in canine adrenal glands in situ, using an autoperfusion system for the adrenal gland that was designed to eliminate indirect central effects of drugs or their metabolites on catecholamine release. The present study documents that GABA modulates the spontaneous release of catecholamines and the release elicited by electrical stimulation of the splanchnic nerve. GABAA receptor agonists such as THIP or muscimol increased the catecholamine content in adrenal effluent blood, whereas bicuculline (0.05 mmol/2 ml min-1), a GABAA receptor antagonist, reduced it. Baclofen (0.094 mmol/2 ml min-1), a GABAB receptor agonist, failed to alter the catecholamine content in adrenal effluent blood. The increased release of catecholamines elicited by 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3[2H]-one (THIP; 0.143 mmol/2 ml min-1) was prevented by bicuculline (0.05 mmol/2 ml min-1) but not by hexamethonium (2.48 mmol/2 ml min-1) or naloxone (0.122 mmol/2 ml min-1). Furthermore, denervation of the adrenal glands failed to prevent the THIP-elicited release of catecholamines.(ABSTRACT TRUNCATED AT 250 WORDS)
D000313:Adrenal Medulla / Q000098:blood supply / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001640:Bicuculline / Q000031:analogs & derivatives / Q000494:pharmacology; D002837:Chromaffin Granules / Q000378:metabolism; D004285:Dogs; D004558:Electric Stimulation; D004837:Epinephrine / Q000097:blood*; D005260:Female; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D006651:Histocytochemistry; D007555:Isoxazoles / Q000494:pharmacology; D009118:Muscimol / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009638:Norepinephrine / Q000097:blood*; D011963:Receptors, GABA-A / Q000378:metabolism*; D013153:Splanchnic Nerves / Q000378:metabolism / Q000502:physiology
D006584:Hexamethonium Compounds; D007555:Isoxazoles; D011963:Receptors, GABA-A; D009118:Muscimol; D009270:Naloxone; D018738:Hexamethonium; C017069:bicuculline methiodide; D001418:Baclofen; C015542:gaboxadol; D009638:Norepinephrine; D001640:Bicuculline; D004837:Epinephrine