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Title: Mechanism through which GABA<inf>A</inf> receptor modulates catecholamine secretion from bovine chromaffin cells
Authors: Gonzalez, M. P.
Oset-Gasque, M. J.
Castro López-Tarruella, Enrique 
Bugeda, J.
Arce, C.
Parramon, M.
UNESCO Clasification: 32 Ciencias médicas
Issue Date: 1992
Publisher: 0306-4522
Journal: Neuroscience 
Abstract: The actions and mechanism of GABAergic modulation of catecholamine secretion from isolated bovine chromaffin cells were investigated. The GABAA receptor agonist muscimol induced a fast rise in cytosolic [Ca2+ ]. The mean peak increase was 290 ± 30nM over basal levels. The increase in cytosolic [Ca2+ ] was abolished in the absence of extracellular [Ca2+ ] and was blocked by the GABAA antagonist bicuculline and the dihydropiridine nifedipine. Muscimol also elicited the release of catecholamines and increased the bisoxonol fluorescence indicating a cell depolarization. The [Ca2+ ] entry was well correlated with muscimol-evoked catecholamine secretion. When cells were treated with muscimol and a second secretagogue, a biphasic behavior was revealed. Muscimol enhanced the catecholamine release evoked by low concentrations of nicotine or K+, whereas release obtained at high concentrations of nicotine or K+ was actually inhibited. When the muscimol effect on membrane potential was studied in the presence of low K+ or nicotine concentrations, an enhancement of the bisoxonol fluorescence was observed. This effect was reversed at high concentrations of both K+ and nicotine. Measurement of 36Cl− fluxes showed an increase in membrane permeability to Cl− during muscimol stimulation. The influx or efflux in Cl− was dependent on membrane potential. In normal conditions, with a K+ concentration of 5.4 mM, a Cl− efflux was observed by both radiometric techniques, with 36Cl− and by the use of the chloride-sensitive fluorescent probe 6-methoxy-N-(3-sulphopropil)quinolinium, as indicator of intracellular Cl−. At high nicotine (20 mM) or K+ concentrations (105 mM) a Cl− influx was observed using 6-methoxy-N-(3-sulphopropil)quinolinium. Equilibrium potential for Cl− was placed at −51.4 ± 2.1mV by independent estimation of 36Cl−distribution across membrane. These results suggest a dual, modulatory role for GABA in the adrenal medulla. Its probable mechanism and implications are discussed.
ISSN: 0306-4522
DOI: 10.1016/0306-4522(92)90263-2
Source: Neuroscience [ISSN 0306-4522], v. 47, p. 487-494
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