Localization of the cGMP-dependent protein kinases in relation to nitric oxide synthase in the brain

The distributions of the type I and type II isoforms of cGMP-dependent protein kinase were determined in the rat brain using immunohistochemistry and in situ hybridization, and compared with the localization of NO synthase determined with NADPH-diaphorase histochemistry. The type I cGMP-dependent protein kinase was highly expressed in the Purkinje cells of the cerebellar cortex, where it was closely associated with the NO synthase containing granule and basket cells. This kinase was also found in neurons in the dorsomedial nucleus of the hypothalamus, where it may be regulated by NO or atriopeptides. The type I kinase was not detected in other central neurons. In contrast, the type II kinase was widely distributed in the brain. In particular, it was highly expressed in the olfactory bulb, cortex, septum, thalamus, tectum and various brainstem nuclei. Many regions expressing this kinase also contained, or received innervation from NO synthase positive neurons. These results indicate that type I cGMP-dependent protein kinase may act as a downstream effector for NO only in the cerebellar cortex and the dorsomedial hypothalamus. The type II cGMP-dependent protein kinase appears to be a major mediator of NO actions in the brain.