DIFFERENTIAL EXPRESSION OF MESSENGER-RNAS FOR PROTEIN-KINASE INHIBITOR ISOFORMS IN MOUSE-BRAIN

Many neurotransmitters are known to regulate neuronal cell function by means of activation of cAMP-dependeht protein kinase (PKA) and phosph orylation of neuronal substrate proteins, including transcription fact ors and ion channels, Here, we have characterized the gene expression of two isoforms of a protein kinase inhibitor (PKI) specific for PKA i n mouse brain by RNase protection and in situ hybridization histochemi stry. The studies demonstrate that the PKI alpha isoform is abundant i n many regions of the adult mouse brain but particularly in cerebellum , hypothalamus, hippocampus, and cortex, In contrast, PKI beta is pres ent at much lower levels in most brain regions but is found in signifi cant amounts in the cerebellum, as well as in distinct nuclei within t he pens, medulla; and hypothalamus. These results are consistent with a regulatory role of endogenous PKI in PKA-mediated signal transductio n in brain and suggest differential functions for the two isoforms of PKI within the central nervous system.