Angiotensin II stimulates activation of Fos-regulating kinase and c-Jun NH2-terminal kinase in neuronal cultures from rat brain.
c-Fos/c-Jun dimers (activating protein-1 transcription factor) are involved in the modulatory actions of angiotensin II (Ang II) on brain norepinephrine neurons, effects mediated via Ang II type 1 (AT1) receptors. The transcriptional activities of c-Fos and c-Jun can be augmented by Fos-regulating kinase (FRK) and c-Jun NH2-terminal kinase (JNK), respectively. In this study, we investigated the effects of Ang II on FRK and JNK activities in neurons cultured from newborn rat hypothalamus and brain stem, which include a population of catecholaminergic cells containing AT1 receptors. Ang II caused time-dependent increases in the activation of FRK and JNK, effects completely inhibited by the AT1 receptor antagonist losartan but not by the Ang II type 2 (AT2) receptor blocker PD123,319. The stimulation of FRK activity by Ang II was abolished by the protein kinase C (PKC) inhibitor GF109203X or the calcium chelator BAPTA, but not by inhibition of calmodulin or calcium/calmodulin-dependent protein kinase II. However, the activation of JNK by Ang II was not dependent on PKC or another calcium-dependent mechanism. These data demonstrate that Ang II stimulates activation of FRK and JNK in neuronal cells, actions that may contribute to the neuromodulatory effects of this peptide.
Huang
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XC
Department of Physiology, College of Medicine, University of Florida, Gainesville 32610, USA.
Deng
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T
Sumners
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C
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000201:enzymology*; D002478:Cells, Cultured; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D009363:Neoplasm Proteins; D009474:Neurons / Q000201:enzymology*; D011493:Protein Kinase C / Q000502:physiology; D011494:Protein Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000502:physiology; D019061:src-Family Kinases
D009363:Neoplasm Proteins; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D011494:Protein Kinases; C490511:Frk protein, rat; D011505:Protein-Tyrosine Kinases; D019061:src-Family Kinases; D011493:Protein Kinase C; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases