NITRIC-OXIDE REGULATES CYCLIC GMP-DEPENDENT PROTEIN-KINASE PHOSPHORYLATION IN RAT-BRAIN

Nitric oxide (NO) acts via soluble guanylyl cyclase to increase cyclic GMP (cGMP), which can regulate various targets including protein kina ses. Western blotting showed that type II cGMP-dependent protein kinas e (cGK II) is widely expressed in various brain regions, especially in the thalamus. In thalamic extracts, the phosphorylation of several pr oteins, including cGK ii, was increased by exogenous NO or cGMP. In vi vo pretreatment with a NO synthase inhibitor reduced the phosphorylati on of cGK II, and this could be reversed by exogenous NO or cGMP. Conv ersely, brainstem electrical stimulation, which enhances thalamic NO r elease, caused a NO synthase-dependent increase in the phosphorylation of thalamic cGK II. These results indicate that endogenous NO regulat es cGMP-dependent protein phosphorylation in the thalamus. The activat ion of cGKII by NO may play a role in thalamic mechanisms underlying a rousal.