Effect of vinconate, an indolonaphthyridine derivative, on metabolism and function of cerebral cholinergic neurons in rat.
Effects of (+/-)-methyl 3-ethyl-2,3,3a,4-tetrahydro-1H-indolo [3,2,1,-de] [1,5] naphthyridine-6-carboxylate hydrochloride (vinconate), an indolonaphthyridine derivative, on the metabolism and function of cerebral cholinergic neurons were investigated using male Wistar rats. Single administration of vinconate (5, 50 and 200 mg/kg) decreased acetylcholine content in the striatum but not those in the cerebral cortex and hippocampus. The same treatment with vinconate (5, 50 and 200 mg/kg, p.o.) had no effect on the activities of choline acetyltransferase and acetylcholinesterase in these brain areas. Although the addition of vinconate (10(-7) - 10(-4) M) had no effect on the high affinity uptake of [3H]choline into striatal slices, it induced a concentration-dependent increase of a KCl(2 x 10(-2) M)-evoked endogenous acetylcholine release. The addition of (-)-sulpiride (10(-8) - 10(-6) M), a dopamine D2 receptor antagonist, also accentuated the KCl(2 x 10(-2) M)-evoked endogenous acetylcholine release form striatal slices. Furthermore, it was found that this (-)-sulpiride (10(-7) M)-induced increase of endogenous acetylcholine release was further augmented by the addition of vinconate (10(-5) M). These results suggest that vinconate may enhance the release of endogenous acetylcholine via the modulation of presynaptic dopamine heteroreceptor in the striatum.
Iino
T
T
Department of Pharmacology, Kyoto Prefectural University of Medicine, Japan.
Katsura
M
M
Kuriyama
K
K
D000109:Acetylcholine / Q000378:metabolism*; D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002794:Choline / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009928:Organ Specificity; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013469:Sulpiride / Q000494:pharmacology; D014748:Vinca Alkaloids / Q000494:pharmacology*
D014748:Vinca Alkaloids; D011189:Potassium Chloride; D013469:Sulpiride; C038627:vinconate; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; D002794:Choline; D000109:Acetylcholine