Stimulating effect of 6R-tetrahydrobiopterin on Ca2+ channels in neurons of rat dorsal motor nucleus of the vagus.
We have recently found that 6R-tetrahydrobiopterin (6R-BH4), a natural cofactor for aromatic L-amino acid hydroxylases and nitric oxide synthase, enhances dopamine release. Here, using a slice patch method, we examined the effect of 6R-BH4 on Ca2+ channels in neurons of rat dorsal motor nucleus of the vagus, where dopaminergic neurons are densely located. 6R-BH4 enhanced N-type Ca2+ channel currents, whereas 6S-BH4, a diastereoisomer of 6R-BH4, had little effect. Neither sodium nitroprusside, a nitric oxide generator, nor L-DOPA, a product of tyrosine hydroxylation, mimicked the effect of 6R-BH4. These findings suggest that 6R-BH4 enhances N-type Ca2+ channel currents in stereospecifically and independently of its cofactor activities as observed in its dopamine releasing action, and raise possibility that 6R-BH4 enhances dopamine release by activating Ca2+ channels.
Shiraki
T
T
First Division, Department of Medicine, Shimane Medical University, Izumo, Japan.
Koshimura
K
K
Kobayashi
S
S
Miwa
S
S
Masaki
T
T
Watanabe
Y
Y
Murakami
Y
Y
Kato
Y
Y
D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives* / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014630:Vagus Nerve / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D015220:Calcium Channels; D001708:Biopterins; C003402:sapropterin