Negative regulation of MAP kinase by diacylglycerol-dependent mechanisms via G protein-coupled receptors in rat basophilic RBL-2H3 (ml) cells.
Carbachol and 5'-(N-ethylcarboxamido)-adenosine (NECA), stimulants of G protein-coupled receptors, induce MAP kinase activation in the muscarinic ml receptor-transfected mast cell line, RBL-2H3 (ml) cells. The phospholipase C inhibitor neomycin and the phosphatidate phosphohydrolase inhibitor propranolol augmented MAP kinase activation induced by carbachol and NECA without affecting the antigen-induced MAP kinase activation. 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 Ro 31-8425 enhanced the carbachol- or NECA-induced MAP kinase activation. These findings suggest that the MAP kinase activation mediated by the G protein-coupled receptors is negatively regulated by diacylglycerol and activated protein kinase C(s).
Hirasawa
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N
Department of Pathophysiological Biochemistry, Faculty of Pharmaceutical Sciences, Tohoku University Sendai, Miyagi, Japan.
Mue
S
S
Ohuchi
K
K
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D002460:Cell Line; D004075:Diglycerides / Q000378:metabolism*; D004140:Dinitrophenols / Q000494:pharmacology; D004791:Enzyme Inhibitors; D019204:GTP-Binding Proteins / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D019950:Mitogen-Activated Protein Kinase 1; D009355:Neomycin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D011976:Receptors, Muscarinic / Q000235:genetics / Q000378:metabolism*; D012709:Serum Albumin / Q000494:pharmacology
D004075:Diglycerides; D004140:Dinitrophenols; D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D011976:Receptors, Muscarinic; D012709:Serum Albumin; C058064:dinitrophenyl-human serum albumin conjugate; C071924:Ro 31-8425; D019830:Adenosine-5'-(N-ethylcarboxamide); D002217:Carbachol; D011433:Propranolol; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D019204:GTP-Binding Proteins; D009355:Neomycin; D000241:Adenosine