Gamma-aminobutyric acid enhancement of potassium-stimulated release of [3H]norepinephrine by multiple mechanisms in rat cortical slices.
Gamma-Aminobutyric acid (GABA) and GABAA agonists enhance stimulated release of [3H]norepinephrine [( 3H]NA) in several regions of the rat brain. In this study, the mechanisms by which GABA and GABAergic agonists augment potassium-stimulated release of [3H]NA from rat frontal cortical slices were examined. GABA enhanced potassium-stimulated [3H]NA release, but did not alter release of [3H]NA evoked by the calcium ionophore A23187, 10(-5) M, either in the presence or the absence of extracellular calcium. The effect of GABA on potassium-stimulated [3H]NA release was apparently reduced by the GABAA antagonist bicuculline methiodide, 10(-4) M, and by the selective inhibitor of GABA uptake SKF 89976A, 10(-5) M, but was abolished only when bicuculline methiodide and SKF 89976A were present in combination. The GABAA agonist muscimol enhanced potassium-stimulated release of [3H]NA in a manner similar to GABA. In addition, nipecotic acid, a substrate for GABA uptake, enhanced potassium-stimulated [3H]NA release. Thus, GABA appears to enhance potassium-stimulated [3H]NA release by acting upon both GABA uptake and GABAA receptors. The GABAA receptors involved in this effect may be a subtype of GABAA receptors since they are not modulated by benzodiazepines. These results support the involvement of the GABA uptake carrier and the GABAA receptor in mediating the enhancement by GABA of potassium-stimulated [3H]NA release in the cortex of the rat.
Peoples
R W
RW
Department of Pharmacology and Toxicology, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, IN 47907-0799.
Giridhar
J
J
Isom
G E
GE
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism; D018756:GABA Antagonists; D066298:In Vitro Techniques; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014316:Tritium; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D018756:GABA Antagonists; D014316:Tritium; D009118:Muscimol; D000001:Calcimycin; D005680:gamma-Aminobutyric Acid; D011188:Potassium; D009638:Norepinephrine