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 subsequent induction of c-fos gene elicited by sustained hypertension in neurons of the nucleus tractus solitarii of anesthetized rats. Activation of glutamate receptors in the nucleus tractus solitarii significantly increased the number of neurons that were immunoreactive to phosphorylated cyclic AMP response element binding protein and Fos protein. Microinjection bilaterally into the nucleus tractus solitarii of the calcium/calmodulin-dependent protein kinase inhibitor, 1-[N,O-bis(5-isoquinolinesulfonyl-N-methyl-L-tyrosyl]-4-phenylpiperazine , appreciably blunted such an increase. This inhibitor also attenuated the augmented immunoreactivity for phosphorylated cyclic AMP response element binding protein or Fos protein in the same nucleus induced by sustained hypertension. These results were comparable to those observed after blockade of either N-methyl-D-aspartate or non-N-methyl-D-aspartate 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 Fos protein induced by sustained hypertension in the nucleus tractus solitarii 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 intracellular events that leads to phosphorylation of cyclic AMP response element binding protein and subsequent induction of c-fos gene after activation of ionotropic glutamate receptors by baroceptive signals in the nucleus tractus solitarii.
Chan
J Y
JY
Department of Medical Education and Research, Veterans General Hospital-Kaohsiung, Taiwan, Republic of China. yhwa@isca.vghks.gov.tw
Chang
J W
JW
Chan
S H
SH
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D017704:Baroreflex / Q000187:drug effects; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000378:metabolism*; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism; D010766:Phosphorylation; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000502:physiology; D017552:Solitary Nucleus / Q000378:metabolism*
D017362:Cyclic AMP Response Element-Binding Protein; D004791:Enzyme Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D017470:Receptors, Glutamate; C063302:KN 62; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D017871:Calcium-Calmodulin-Dependent Protein Kinases