Pharmacological evidence for the possible involvement of repetitive action potentials in facilitation by GABA of catecholamine secretion in bovine adrenal chromaffin cells.
1. gamma-Aminobutyric acid (GABA) evokes catecholamine (CA) secretion and enhances the stimulation-evoked CA secretion via facilitation of Ca2+ entry in a Cl(-)-dependent manner. The present study was designed to investigate further the ionic mechanism of modulation by GABA of CA secretion from adrenal medulla, using a primary culture of bovine chromaffin cells. 2. Tetrodotoxin (TTX), a voltage-sensitive Na+ channel blocker, reduced GABA-evoked CA secretion. 3. Inhibition of the sodium pump by ouabain or removal of extracellular K+ enhanced GABA-evoked CA secretion in a TTX-sensitive manner. 4. Tetraethylammonium (TEA) and cesium, which are known to block some types of K+ channels, markedly enhanced GABA-evoked CA secretion in a concentration-related fashion. TEA-induced enhancement of the GABA-evoked CA secretion was attenuated by TTX or replacement of extracellular Na+ by choline. On the other hand, ouabain accelerated the effect of TEA. 5. TEA and ouabain also enhanced GABA-induced Ca2+ influx and accumulation of cytosolic Ca2+, assessed with 45Ca2+ uptake and quin2 fluorescence. 6. Veratridine increased accumulation of cytosolic Ca2+ in a TTX-sensitive manner. GABA facilitated the veratridine-induced elevation of cytosolic Ca2+ even when the GABA-induced rise of cytosolic Ca2+ levelled off. 7. These results suggest the involvement of repetitive action potentials in modulation of GABA by Ca2+ mobilization and, as a consequence, of the CA secretion in chromaffin cells.
Department of Pharmacology, Hiroshima University School of Dentistry, Japan.
S
S
Kitayama
Y
Y
Nakatsukasa
K
K
Morita
T
T
Dohi
A
A
Tsujimoto
D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D002837:Chromaffin Granules / Q000378:metabolism* / Q000502:physiology; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D002395:Catecholamines; D013757:Tetraethylammonium Compounds; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D002118:Calcium