A novel action of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin, a cofactor for hydroxylases of phenylalanine, tyrosine and tryptophan: enhancement of acetylcholine release in vivo in the rat hippocampus.
Recently, we have reported that 6R-L-erythro-tetrahydrobiopterin (6R-BH4), a natural cofactor for hydroxylases of phenylalanine, tyrosine and tryptophan, has a dopamine releasing action in the rat striatum independent of its cofactor role. Here we studied the effects of 6R-BH4 on acetylcholine (ACh) release in the rat hippocampus using brain microdialysis. Intracerebroventricular injection of 6R-BH4 dose-dependently increased extracellular ACh levels monitored by brain microdialysis. Biopterin, an oxidized form of 6R-BH4, and 6S-BH4, an unnatural diastereoisomer of 6R-BH4, had little effect on the ACh levels. The 6R-BH4-induced increase in ACh levels was eliminated after inhibition of voltage-dependent Na+ channels by tetrodotoxin, but not after depletion of catecholamines by reserpine. These results show that 6R-BH4 has direct ACh releasing action in vivo.
Ohue
T
T
Department of Pharmacology, Kyoto University Faculty of Medicine, Japan.
Koshimura
K
K
Lee
K
K
Watanabe
Y
Y
Miwa
S
S
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D002794:Choline / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003956:Dialysis / Q000379:methods; D006624:Hippocampus / Q000378:metabolism*; D007276:Injections, Intraventricular; D008297:Male; D006899:Mixed Function Oxygenases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012110:Reserpine / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014364:Tryptophan / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D001708:Biopterins; D014443:Tyrosine; D013779:Tetrodotoxin; D012110:Reserpine; D014364:Tryptophan; D006899:Mixed Function Oxygenases; C003402:sapropterin; D002794:Choline; D000109:Acetylcholine