THE ACTIVATION OF P38 MAPK BY THE BETA-ADRENERGIC AGONIST ISOPROTERENOL IN RAT EPIDIDYMAL FAT-CELLS

Here we report that the beta-adrenergic agonist isoproterenol increase s the activity of the stress-activated kinase p38 MAPK over 10-fold in freshly isolated rat epididymal fat cells. Stimulation of the kinase was rapid, sustained for at least 60 min and sensitive to the specific p38 MAPK inhibitor, SE 203580, Half-maximal stimulation of p38 MAPK b y isoproterenol occurred at 13 nM isoproterenol. The cell permeable cy clic AMP analogue, chlorophenylthio-cyclic AMP increased p38 MAPK acti vity to a similar er;tent to isoproterenol, suggesting that the effect of the beta-adrenergic agonist is mediated via increases in the activ ity of cyclic-AMP dependent protein kinase, Although it had little or no effect on the activity of c-Jun N-terminal kinase, isoproterenol an d a number of other treatments which activated p38 MAPK were found to stimulate AR;activated protein kinase in fat cells, Activation of AMPK and p38 MAPK were not, however, found to be directly linked. (C) 1998 Federation of European Biochemical Societies.