GABAergic modulation of catecholamine release from cultured bovine adrenal chromaffin cells. Evidence for the involvement of Cl(-)-dependent Ca2+ entry.
The mode by which GABA facilitates the basal and stimulation-evoked catecholamine (CA) release from cultured bovine adrenal chromaffin cells was investigated. Muscimol, a GABAA receptor agonist, facilitated 45Ca uptake in a concentration-related manner. When GABA and acetylcholine (ACh) were simultaneously applied, additive increase in 45Ca uptake was observed. Similar effect on 45Ca uptake was observed in the presence of GABA and veratridine, although 45Ca uptake induced by a rather low concentration of veratridine was more than additively enhanced by GABA. GABA-evoked CA release was also more than additively enhanced by BayK 8644 whereas there was only an additive effect on 45Ca uptake. Substitution of extracellular Cl- by sucrose ("low Cl- medium") during the stimulation with GABA enhanced GABA-evoked CA release. Substitution of extracellular Cl- for more than 1 h abolished GABA-evoked CA release and 45Ca uptake. At this time, the concentration-response curve for veratridine-evoked CA release was shifted to left and GABA no longer enhanced veratridine-evoked CA release at any concentration of veratridine. GABA-induced facilitation of 45Ca uptake in the presence of low concentration of veratridine was also inhibited by long-term treatment with low Cl- medium. These results suggest that the Cl(-)-dependent process linked to GABAA receptor acts on voltage-sensitive Ca2+ channels in chromaffin cells to elicit and modulate CA release.
Department of Pharmacology, Hiroshima University, School of Dentistry, Japan.
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S
Kitayama
K
K
Morita
T
T
Dohi
A
A
Tsujimoto
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000311:Adrenal Glands / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000493:pharmacokinetics; D002132:Calcium Radioisotopes; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D002712:Chlorides / Q000494:pharmacology; D002838:Chromaffin System / Q000166:cytology / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007473:Ion Channels / Q000187:drug effects; D009118:Muscimol / Q000494:pharmacology; D010424:Pentobarbital / Q000494:pharmacology; D013997:Time Factors; D014701:Veratridine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology* / Q000502:physiology
D002132:Calcium Radioisotopes; D002395:Catecholamines; D002712:Chlorides; D007473:Ion Channels; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D014701:Veratridine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D010424:Pentobarbital; D000109:Acetylcholine; D002118:Calcium