Effects of NADH on dopamine release in rat striatum.
Nicotinamide adenine dinucleotide (NADH) may be utilized for the synthesis and regeneration of tetrahydrobiopterin (BH(4)), which in turn is an essential cofactor for tyrosine hydroxylase, the rate-limiting enzyme in the synthesis of dopamine (DA). NADH has been reported to relieve some of the symptoms of Parkinson's disease, presumably by altering dopaminergic function. The present study examines the efficacy of NADH in influencing DA activity in the rat striatum. In striatal slices, NADH (350 microM) significantly increased basal DA and DOPAC efflux and caused a 2-fold increase in the DA overflow evoked by high KCl (25 mM). Tissue levels of BH(4), basal BH(4) efflux, and KCl-evoked BH(4) overflow were unaffected by NADH, as was [(3)H]DA uptake into striatal synaptosomes. In contrast to the effects of NADH on DA function in vitro, no effects were observed when NADH was administered systemically. NADH (10 or 100 mg/kg, s.c.) did not influence the tissue content of DA, 5-HT, or their metabolites in the midbrain or striatum, nor did it alter DA extracellular concentrations. These results indicate that NADH can increase DA release from striatal slices, although we are as yet unable to detect this effect in vivo.
Pearl
S M
SM
Departments of Neurology and Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
Antion
M D
MD
Stanwood
G D
GD
Jaumotte
J D
JD
Kapatos
G
G
Zigmond
M J
MJ
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001708:Biopterins / Q000031:analogs & derivatives / Q000378:metabolism; D018929:Cell Culture Techniques; D004298:Dopamine / Q000378:metabolism*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009243:NAD / Q000378:metabolism* / Q000494:pharmacology*; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000975:Antioxidants; D009243:NAD; D001708:Biopterins; D011189:Potassium Chloride; C003402:sapropterin; D004298:Dopamine