Stimulatory effect of γ-aminobutyric acid on catecholamine release from isolated perfused dog adrenals

Abstract

Recently it has been shown that γ-aminobutyric acid (GABA) and related enzymes exist in mammalian sympathetic ganglia, and GABA depresses transmission associated with a depolarization in this tissue. Therefore possible involvement of GABA in catecholamine (CA) release from adrenal medulla, which develop from primitive cells of the sympathetic ganglia, was investigated. GABA (10−6-10−4M) released CA from isolated perfused adrenal glands of dogs in the dose-dependent manner and no tachyphylaxis to the releasing effect was observed. GABA agonists, 3-amino-l-propane-sulfonic acid (3-APS, 10−6-10−4M), imidazole-4-acetic acid (10−5-10−3M) also dose-dependently stimulated CA release. GABA antagonist, bicucu-lline (3×10−5M), markedly inhibited CA release induced by GABA (3×10−5M) and 3-APS (3×10−5M), but did not reduce the effect of acetylcholine (ACh, 5×10−6M). Pretreatment of 2.5×10−5M atropine plus 5×10−5M hexamethonium, which completely inhibit the effect of ACh, did not influence the effect of GABA. GABA-induced CA release was abolished by the removal of Ca2+ from perfusion medium, but was not reduced by the removal of Na+ or Cl− Ca2+ antagonists, verapamil (5×10−5M), CoCl2 (3×l0−3M) and dibucaine (10−4M) markedly depressed the effect of GABA. Tetrodotoxin (2−10−7M), a Na channel blocker, which completely inhibited CA release induced by vereratridine (7.5×10−6M), did not reduce GABA evoked CA release. These results suggest that GABA may interact with its receptors to evoke CA release depending on external CaZ+ in dog adrenal medulla.