The regulation of dopamine release from striatum slices by tetrahydrobiopterin and L-arginine-derived nitric oxide.
The regulation of dopamine release by 6(R)-tetrahydrobiopterin (BH4) and l-arginine-derived nitric oxide was examined by using a method of superfusion of rat striatum slices in vitro. l-Arginine, which can produce nitric oxide (NO) through the action of NO synthase, induces a concentration-dependent increase of [3H] dopamine release in the superfusate of striatum slices. Pretreatment with inhibitors of NO synthase or with inhibitors of BH4 synthesis diminishes the increase of [3H] dopamine release mediated by arginine. This increase is almost completely restored following repletion of intracellular BH4 levels by incubation of the slices with 7, 8-dihydrobiopterin. Adding exogenous BH4 directly to the superfusion fluid leads to a massive increase in [3H] dopamine release which can be inhibited 75% by superoxide dismutase and catalase, but is not inhibited by NG-nitro-arginine, a NO synthase inhibitor, or alpha-methyl-p-tyrosine, a tyrosine hydroxylase inhibitor. The increase of intracellular BH4 concentration by dihydrobiopterin administration causes a small increase of dopamine release which can be partially diminished by NG-nitro-arginine or alpha-methyl-p-tyrosine. It is suggested that the increase of dopamine release stimulated by an enhancement of intracellular BH4 is dependent on its cofactor activity with NO synthase and tyrosine hydroxylase. This study has also demonstrated that BH4 is a regulator of NO-mediated dopamine release in the striatum. Published by Elsevier Science B.V.
Laboratory of Neurochemistry, National Institute of Mental Health, 36 Convent Dr. MSC 4096, Bldg. 36 Rm 3D/30, Bethesda, MD 20892, USA.
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D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001120:Arginine / Q000494:pharmacology*; D001708:Biopterins / Q000031:analogs & derivatives* / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology*; D004232:Diuretics / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004976:Ethacrynic Acid / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D013400:Sugar Acids / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000494:pharmacology; D014316:Tritium; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors / Q000378:metabolism
C017182:5-dehydro-3-deoxy-D-arabino-heptulosonic acid-7-phosphate; D000975:Antioxidants; D004232:Diuretics; D013400:Sugar Acids; D014316:Tritium; D013481:Superoxides; D001708:Biopterins; D009569:Nitric Oxide; C017226:7,8-dihydrobiopterin; D001120:Arginine; D002374:Catalase; D019001:Nitric Oxide Synthase; D014446:Tyrosine 3-Monooxygenase; D013482:Superoxide Dismutase; C003402:sapropterin; D004976:Ethacrynic Acid; D004298:Dopamine