α1- and β-adrenoceptor stimulation differentially activate p38-MAPK and atrial natriuretic peptide production in the perfused amphibian heart

SUMMARY We investigated the activation of p38-MAPK by various adrenergic agents in the perfused Rana ridibunda heart. Phenylephrine (50 μmol l-1) rapidly induced the differential activation of all three mitogen-activated protein kinase (MAPK) subfamilies (ERK, JNKs and p38-MAPK)in this experimental system. Focusing on p38-MAPK response to phenylephrine,we found that the kinase phosphorylation reached maximal values at 30 s,declining thereafter to basal values at 15 min. p38-MAPK activation by phenylephrine was verified as exclusively α1-AR-mediated. Furthermore, SB203580 (1 μmol l-1) abolished the kinase phosphorylation by phenylephrine. Isoproterenol (50 μmol l-1)was also shown to activate p38-MAPK in a time- and temperature-dependent manner. A marked, sustained p38-MAPK activation profile was observed at 25°C, while at 18°C the kinase response to isoproterenol was modest. Isoproterenol effect on p38-MAPK stimulation was β-AR-mediated. Immunohistochemical studies revealed the enhanced presence of phosphorylated p38-MAPK and atrial natriuretic peptide (ANP) in both phenylephrine- and isoproterenol-stimulated hearts, a reaction completely blocked by the respective specific antagonists, or the specific p38-MAPK inhibitor SB203580. These findings indicate a functional correlation between p38-MAPK activation and ANP accumulation in the perfused amphibian heart.