IMPAIRMENT OF THE NITRIC-OXIDE CYCLIC-GMP PATHWAY IN CEREBELLAR SLICES PREPARED FROM THE HPH-1 MOUSE

In this study, the effect of tetrahydrobiopterin deficiency on the nit ric oxide/cGMP pathway has been investigated in cerebellar slices deri ved from the hph-1 mouse. This animal displays a partial deficiency of tetrahydrobiopterin. Basal levels of cGMP were significantly reduced (-29.5%) in the hph-1 mouse cerebellum compared to controls. Following kainate stimulation (500 mu M) cGMP levels increased in both control and hph-1 preparations but were again significantly lower (-29.1%) in the hph-1 mouse. Exposure of slices to the nitric oxide donors, S-nitr oso-N-acetylpenicillamine and S-nitroso-glutathione, revealed no diffe rence in cGMP accumulation between the two groups. These findings sugg est that the cerebellar nitric oxide/cGMP pathway may be impaired in p artial tetrahydrobiopterin deficiency states due to diminished nitric oxide formation.