| Research Abstract |
We investigated the role of gamma-aminobutyric acid (GABA) in catecholamine (CA) release from adrenal medulla using a primary culture of bovine adrenal chromaffin cells. 1. GABA elicited CA release from monolayer cultures of bovine adrenal chromaffin cells, and facilitated acetylcholine (ACh)-evoked CA release via GABA receptor. Benzodiazepines and pentbarbital enhanced the action of GABA. 2. GABA caused an increase in ^<45>Ca uptake associated with CA release. Ach-induced ^<45>Ca uptake was additively enhanced by GABA, whereas veratridine (at low concentration)- evoked ^<45>Ca uptake was more than additively enhanced by GABA. 3. GABA-evoked ^<45>Ca uptake and CA release were modified by replacing extracellular C1^- by impermeable anion or sucrose in a time-related fashion: sudden replacement of extracellular C^- by sucrose enhanced GABA-evoked CA release whereas long-term treatment with low C1^- medium reduced GABA-evoked CA release and ^<45>Ca uptake. 4. GABA increased bis-oxonol fluorescence, reflecting a depolarization of chromaffin cells. Furthermore, GABA caused an increase in cytosolic Ca^<2+> ([Ca^<2+>]i), assessed by quin2. GABA-induced depolarization and rise of [Ca^<2+>]i were well correlated with ^<45>Ca uptake and CA release.
Based on these results, we concluded that GABA causes an influx of Ca^<2+> through voltage- gated Ca^<2+> channels as a consequence of depolarization via C1^--dependent mechanism. This, in turn, elicited [Ca^<2+>]i rise leading to an exocytotic release of CA by GABA itself and to an facilitatory modulation by GABA of stimulation-evoked CA release.
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