STIMULATING EFFECT OF 6R-TETRAHYDROBIOPTERIN ON CA(2+) 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 synt hase, enhances dopamine release. Here, using a slice patch method, we examined the effect of 6R-BH4 on Ca2+ channels in neurons of rat dorsa l motor nucleus of the vagus, where dopaminergic neurons are densely l ocated. 6R-BH4 enhanced N-type Ca2+ channel currents, whereas 6S-BH4, a diastereoisomer of 6R-BH4, had little effect. Neither sodium nitropr usside, a nitric oxide generator, nor L-DOPA, a product of tyrosine hy droxylation, mimicked the effect of 6R-BH4. These findings suggest tha t 6R-BH4 enhances N-type Ca2+ channel currents in stereospecifically a nd independently of its cofactor activities as observed in its dopamin e releasing action, and raise possibility that 6R-BH4 enhances dopamin e release by activating Ca2+ channels. (C) 1996 Academic Press, Inc.