NEGATIVE REGULATION OF MAP-KINASE BY DIACYLGLYCEROL-DEPENDENT MECHANISMS VIA G-PROTEIN-COUPLED RECEPTORS IN RAT BASOPHILIC RBL-2H3(M1)-CELLS

Carbachol and 5'-(N-ethylcarboxamido)-adenosine (NECA), stimulants of G protein-coupled receptors, induce MAP kinase activation in the musca rinic ml receptor-transfected mast cell line, RBL-2H3 (mi) cells. The phospholipase C inhibitor neomycin and the phosphatidate phosphohydrol ase inhibitor propranolol augmented MAP kinase activation induced by c arbachol and NECA without affecting the antigen-induced MAP kinase act ivation. Furthermore, the duration of MAP kinase activation induced by carbachol or NECA was also prolonged by neomycin and propranolol. The specific protein kinase C inhibitor Po 31-8425 enhanced the carbachol - or NECA-induced MAP kinase activation. These findings suggest that t he MAP kinase activation mediated by the G protein coupled receptors i s negatively regulated by diacylglycerol and activated protein kinase C(s). (C) 1997 Elsevier Science Inc.