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Pharmacological evidence for the possible involvement of repetitive action potentials in facilitation by GABA of catecholamine secretion in bovine adrenal chromaffin cells
Author(s) -
Kitayama Shigeo,
Nakatsukasa Yoichi,
Morita Katsuya,
Dohi Toshihiro,
Tsujimoto Akira
Publication year - 1991
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1991.tb12237.x
Subject(s) - veratridine , adrenal medulla , tetrodotoxin , secretion , ouabain , catecholamine , endocrinology , medicine , chromaffin cell , chemistry , extracellular , biophysics , biology , sodium channel , sodium , biochemistry , organic chemistry
1 γ‐Aminobutyric acid (GABA) evokes catecholamine (CA) secretion and enhances the stimulation‐evoked CA secretion via facilitation of Ca 2+ 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 Ca 2+ influx and accumulation of cytosolic Ca 2+ , assessed with 45 Ca 2+ uptake and quin2 fluorescence. 6 Veratridine increased accumulation of cytosolic Ca 2+ in a TTX‐sensitive manner. GABA facilitated the veratridine‐induced elevation of cytosolic Ca 2+ even when the GABA‐induced rise of cytosolic Ca 2+ levelled off. 7 These results suggest the involvement of repetitive action potentials in modulation of GABA by Ca 2+ mobilization and, as a consequence, of the CA secretion in chromaffin cells.