Alpha(1)- and beta-adrenoceptor stimulation differentially activate p38-MAPK and atrial natriuretic peptide production in the perfused amphibian heart.
We investigated the activation of p38-MAPK by various adrenergic agents in the perfused Rana ridibunda heart. Phenylephrine (50 micromol 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 alpha(1)-AR-mediated. Furthermore, SB203580 (1 micromol l(-1)) abolished the kinase phosphorylation by phenylephrine. Isoproterenol (50 micromol 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 degrees C, while at 18 degrees C the kinase response to isoproterenol was modest. Isoproterenol effect on p38-MAPK stimulation was beta-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.
Aggeli
Ioanna-Katerina S
IK
Department of Animal and Human Physiology, School of Biology, Faculty of Sciences, University of Athens, Panepistimioupolis, Athens, Greece.
Gaitanaki
Catherine
C
Lazou
Antigone
A
Beis
Isidoros
I
D000322:Adrenergic Agonists / Q000494:pharmacology; D058646:Adrenergic alpha-1 Receptor Agonists; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis*; D015153:Blotting, Western; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation; D007093:Imidazoles / Q000494:pharmacology; D007150:Immunohistochemistry; D007545:Isoproterenol / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D010477:Perfusion; D010656:Phenylephrine / Q000494:pharmacology; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D011895:Rana ridibunda; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases
D000322:Adrenergic Agonists; D058646:Adrenergic alpha-1 Receptor Agonists; D007093:Imidazoles; D011725:Pyridines; D018340:Receptors, Adrenergic, alpha-1; D011943:Receptors, Adrenergic, beta; D010656:Phenylephrine; D009320:Atrial Natriuretic Factor; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D007545:Isoproterenol; C093642:SB 203580