Role of calcium/calmodulin-dependent protein kinases in expression of fos protein in the nucleus tractus solitarii after sustained hypertension

We investigated the role of calcium/calmodulin-dependent protein kinases in the phosphorylation of cyclic AMP response element binding protein and sub sequent induction of c-fos gene elicited by sustained hypertension in neuro ns of the nucleus tractus solitarii of anesthetized rats. Activation of glu tamate receptors in the nucleus tractus solitarii significantly increased t he number of neurons that were immunoreactive to phosphorylated cyclic AMP response element binding protein and Fos protein. Microinjection bilaterall y into the nucleus tractus solitarii of the calcium/calmodulin-dependent pr otein kinase inhibitor, 1-[N,O-bis(5-isoquinolinesulfonyl-N-methyl-L-tyrosy l]-4-phenylpiperazine, appreciably blunted such an increase. This inhibitor also attenuated the augmented immunoreactivity for phosphorylated cyclic A MP response element binding protein or Fos protein in the same nucleus indu ced by sustained hypertension. These results were comparable to those obser ved after blockade of either N-methyl-D-aspartate or non-N-methyl-D-asparta te ionotropic glutamate receptors in the nucleus tractus solitarii. Reverse transcription-polymerase chain reaction further indicated that the calcium /calmodulin-dependent protein kinase blocker attenuated the expression of F os protein induced by sustained hypertension in the nucleus tractus solitar ii by suppressing the transcription of c-fos messenger RNA. The present results suggest that activation of calcium/calmodulin-dependent protein kinases may represent an important step in the cascade of intracel lular events that leads to phosphorylation of cyclic AMP response element b inding protein and subsequent induction of c-fos gene after activation of i onotropic glutamate receptors by baroceptive signals in the nucleus tractus solitarii, (C) 1999 IBRO. Published by Elsevier Science Ltd.