title: Mechanism through which GABAA receptor modulates catecholamine secretion from bovine chromaffin cells.
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)
authors.affiliation: Instituto de Bioquìmica, Centro mixto C.S.I.C.-U.C.M., Fac. de Farmacia, Univesidad Complutense, Madrid, Spain.
authors.forename: M P
authors.initials: MP
authors.lastname: Gonzalez
authors.forename: M J
authors.initials: MJ
authors.lastname: Oset-Gasque
authors.forename: E
authors.initials: E
authors.lastname: Castro
authors.forename: J
authors.initials: J
authors.lastname: Bugeda
authors.forename: C
authors.initials: C
authors.lastname: Arce
authors.forename: M
authors.initials: M
authors.lastname: Parramon
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002712:Chlorides / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004759:Enterochromaffin Cells / Q000187:drug effects / Q000378:metabolism*; D005453:Fluorescence; D066298:In Vitro Techniques; D008564:Membrane Potentials; D009118:Muscimol / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology; D011806:Quinolinium Compounds / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*
chemical_list: D002395:Catecholamines; D002712:Chlorides; D011806:Quinolinium Compounds; D011963:Receptors, GABA-A; D009118:Muscimol; D009538:Nicotine; C052335:6-methoxy-N-(3-sulfopropyl)quinolinium; D002118:Calcium