Presynaptic mechanisms underlying the gamma-aminobutyric acid-evoked receptor-independent release of [3H]norepinephrine in rat hippocampus.
The effects of gamma-aminobutyric acid (GABA) on the spontaneous efflux of [3H]norepinephrine ([3H]NE) were studied in synaptosomes prepared from rat hippocampus and prelabelled with [3H]NE. It had been observed previously that, when synaptosomes were exposed in superfusion to GABA, the basal release of the tritiated catecholamine was enhanced, apparently with no involvement of the known GABA receptors. The mechanisms underlying this effect have now been investigated. The potency of GABA as a releaser of [3H]NE was decreased by lowering the Na+ content of the superfusion medium, and its effect disappeared at 23 mM Na+. The GABA-induced [3H]NE release was counteracted by the GABA uptake inhibitor N-(4,4-diphenyl-3-butenyl)nipecotic acid (SKF 89976A), but it was unaffected by the NE uptake blockers desmethylimipramine and nisoxetine. The GABA-induced release of [3H]NE was Ca2+-dependent and tetrodotoxin-sensitive. The data support the hypothesis that GABA provoked [3H]NE release by a novel mechanism which involves penetration into the noradrenergic nerve terminals through a GABA carrier located on the NE terminals themselves. This uptake process might be electrogenic and provoke depolarization of the nerve terminals, causing an exocytotic release of [3H]NE.
Bonanno
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Istituto di Farmacologia e Farmacognosia, Università degli Studi di Genova, Italy.
Fontana
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G
Fedele
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E
Robino
G
G
Raiteri
M
M
D000818:Animals; D001696:Biomechanical Phenomena; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D009557:Nipecotic Acids / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D011392:Proline / Q000031:analogs & derivatives*; D051381:Rats; D011919:Rats, Inbred Strains; D017981:Receptors, Neurotransmitter / Q000502:physiology; D012964:Sodium / Q000494:pharmacology; D013569:Synapses / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014316:Tritium; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D009557:Nipecotic Acids; D017981:Receptors, Neurotransmitter; D014316:Tritium; C030278:nipecotic acid; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; C045598:N-(4,4-diphenyl-3-butenyl)nipecotic acid; D011392:Proline; D012964:Sodium; C010983:homoproline; D009638:Norepinephrine