1322511

Mechanism through which GABAA receptor modulates catecholamine secretion from bovine chromaffin cells.

Article date: 1992/1/1

PubMed ID: 1322511

Journal name: Neuroscience (ISSN: 0306-4522)

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 +/- 30 nM 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.(ABSTRACT TRUNCATED AT 250 WORDS)

This document is available from: http://directlinks.cc/files/muscimol/1322511.pdf

Author List: Gonzalez M P, Oset-Gasque M J, Castro E, Bugeda J, Arce C, Parramon M

Publication Types: Journal Article; Research Support, Non-U.S. Gov't

Substances mentioned in the article: Catecholamines; Chlorides; Quinolinium Compounds; Receptors, GABA-A; Muscimol; Nicotine; 6-methoxy-N-(3-sulfopropyl)quinolinium; Calcium;

Mesh terms: Animals; Calcium/metabolism; Catecholamines/metabolism; Cattle; Chlorides/metabolism; Cytosol/metabolism; Enterochromaffin Cells/drug effects; Fluorescence; In Vitro Techniques; Membrane Potentials; Muscimol/pharmacology; Nicotine/pharmacology; Quinolinium Compounds/pharmacology; Receptors, GABA-A/drug effects;

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