STIMULATION OF 42 44 KDA MITOGEN-ACTIVATED PROTEIN-KINASES BY ARGININE-VASOPRESSIN IN RAT CARDIOMYOCYTES/

Vasoconstrictors, such as angiotensin IT (Ang II), are involved in the regulatory mechanisms of post myocardial infarction (MI) hypertrophy. Arginine vasopressin (AVP), may be another vasoconstrictor that influ ences the mechanisms that lead to post MI hypertrophy. In these studie s we investigated the possible activation of the 42/44 kDa mitogen-act ivated protein kinases (MAPKs), also referred as extracellular signal regulated kinases (ERKs), in cultured cardiomyocytes. Treatment of rat cardiomyocytes with AVP, Ang II and phorbol 12-myristate 13-acetate ( PMA) increases the activation of ERKs. The activity of the 42/44 kDa M APKs was tested using the phosphorylation of: (1) EGF receptor peptide (EGFR-P); (2) myelin basic protein (MBP) immobilized in poly acrylami de gels; and (3) T-183 and Y-185 residues of these proteins. The activ ity of the MAPKs, induced by AVP or PMA was inhibited by downregulatio n of protein kinase C (PKC), by the tyrosine kinase inhibitor genistei n and by MAPK kinase (MEK) inhibitor, PD98059. In addition, the AVP-in duced stimulation of MAPKs was shown to be mediated through a V-1 rece ptor. We suggest that AVP activates the 42/44kDa MAPKs through a signa l transduction pathway that involves stimulation of AVP-V-1 receptor, tyrosine kinase, PKC and MEK. These results suggest that AVP may be in volved in ERKs dependent regulatory functions of cardiomyocytes growth . (C) 1998 Elsevier Science B.V.