Pharmacological evidence for the possible involvement of repetitive action potentials in facilitation by GABA of catecholamine secretion in bovine adrenal chromaffin cells

Abstract

γ‐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. Tetrodotoxin (TTX), a voltage‐sensitive Na+ channel blocker, reduced GABA‐evoked CA secretion. Inhibition of the sodium pump by ouabain or removal of extracellular K+ enhanced GABA‐evoked CA secretion in a TTX‐sensitive manner. 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. TEA and ouabain also enhanced GABA‐induced Ca2+ influx and accumulation of cytosolic Ca2+, assessed with 45Ca2+ uptake and quin2 fluorescence. 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. 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.

Role of Cl–Co-Transporters in the Excitation Produced by GABAAReceptors in Juvenile Bovine Adrenal Chromaffin Cells

“…Consistent with these observations, blockade of NKCC1 with bumetanide significantly shifted E Cl , as measured by changes in [Ca 2ϩ ] i . As discussed above, there is still considerable debate about whether activation of GABA A receptors in chromaffin cells inhibits the excitation produced by the physiological activator of chromaffin cells, ACh (Fujimoto et al 1987;Kataoka et al 1986;Kitayama et al 1990cKitayama et al , 1991. Our results suggest that activation of GABA A receptors in chromaffin cells is excitatory under all conditions.…”

“…In some cells, activation of GABA A receptors is depolarizing but is still inhibitory (Zhang and Jackson 1993). In chromaffin cells, there is considerable controversy whether GABA can inhibit responses to high K ϩ or ACh, even though GABA itself is excitatory (Fujimoto et al 1987;Kataoka et al 1986;Kitayama et al 1990cKitayama et al , 1991. To address this issue, we examined elevations in [Ca 2ϩ ] i in response to ACh, in the presence and absence of muscimol, to determine whether activation of GABA A receptors would inhibit the response to ACh.…”

“…Sangiah et al (1974) first showed that GABA could elicit catecholamine release from isolated perfused adrenal glands, a result that has been repeated (Fujimoto et al 1987;Kataoka et al 1984;Kitayama et al 1984). Even though a variety of studies have demonstrated that GABA depolarizes chromaffin cells, there is still a question of whether the net effect of GABA is excitatory or inhibitory; some studies suggest that GABA acts to inhibit excitation produced by acetylcholine (Ach) or high K ϩ (Fujimoto et al 1987;Kataoka et al 1986), while other studies suggest that GABA facilitates stimulation evoked release (Kitayama et al 1990c(Kitayama et al , 1991.…”

Colocalization of Gamma-Aminobutyric Acid Immunoreactivity and Acetylcholinesterase Activity in Nerve Fibers of the Mouse Adrenal Gland.

“…These findings suggest that GABA and acetylcholine are colocalized in the same nerve fibers and are released from them. Previous physiological study showed that GABA induced release of catecholamines from the chromaffin cells [1,[14][15][16], and that the GABA-induced secretory response is a consequence of the Ca 2+ influx through voltage-sensitive Ca 2+ channels in a Cl -depending manner [18,19]. Furthermore, it is generally accepted that acetylcholine stimulates release of catecholamine from the chromaffin cells.…”

GABA Has Excitatory Actions on GnRH-Secreting Immortalized Hypothalamic (GT1-7) Neurons

“…For example, GABA depolarizes rodent sympathetic ganglia [42,43]. Application of GABA to bovine adrenal chromaffin cells activates action potentials [44] and increases [Ca2+]j [45,46], GABA-evoked repetitive action potentials are thought to facilitate catecholamine secretion from chro maffin cells by elevating cytosolic Ca2+ levels [47], Simi larly, the excitatory action of GABA on GT1-7 cells is probably responsible for the GABA-induced increase of GnRH secretion from these cells [12] and may explain the stimulatory actions of GABA on GnRH release from hypothalamic slices [7], Activation of a bicuculline-insensitive GABAa receptor has also been reported to stimulate LH release from female rat pituitary cells. This effect was mimicked by the selective GABAa receptor agonist mus cimol and was inhibited by voltage-activated Ca2+ chan nel blockers [48].…”