Stimulation of receptors of gamma-aminobutyric acid modulates the release of cholecystokinin-like immunoreactivity from slices of rat neostriatum.
Slices of rat dorsal neostriatum were incubated in Krebs-Henseleit medium and the release of cholecystokinin-like immunoreactivity (CCK-IR) was induced by veratridine or high concentrations of K+. It was investigated whether drugs which act at receptors for gamma-aminobutyric acid (GABA) affected the release. The GABAA-receptor agonists muscimol and isoguvacine enhanced the veratridine-induced release of CCK-IR. This effect was abolished by the GABAA-receptor antagonist, bicuculline. When used alone, bicuculline decreased the release. The GABAB-receptor agonist, (-)-baclofen, decreased the veratridine-induced release of CCK-IR. The stereoisomer (+)-baclofen, which has low intrinsic activity, had no effect when used alone, but antagonized the effect of (-)-baclofen as did delta-amino-n-valeric acid, another antagonist at GABAB-receptors. When the release of CCK-IR was stimulated by K+ (40 mM) in the presence of tetrodotoxin, it was no longer affected by GABAA-receptor agonists or antagonists. Thus, their sites of action were probably not in the immediate vicinity of the nerve-endings which release CCK-IR. Under these conditions, stimulation of GABAB-receptors still reduced the release of CCK-IR. Therefore, it is concluded that these receptors are in the immediate vicinity of or even on the terminals which release CCK-IR.
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D002421:Caudate Nucleus / Q000378:metabolism*; D002766:Cholecystokinin / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D066298:In Vitro Techniques; D009118:Muscimol / Q000494:pharmacology; D011699:Putamen / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects*; D013237:Stereoisomerism; D013779:Tetrodotoxin / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology
D011963:Receptors, GABA-A; D009118:Muscimol; D013779:Tetrodotoxin; D014701:Veratridine; D002766:Cholecystokinin; D001418:Baclofen