3',5'-cyclic guanosine monophosphate activates mitogen-activated protein kinase in rat pinealocytes.
The role of 3',5'-cyclic guanosine monophosphate (cGMP) in the activation of mitogen-activated protein kinases (MAPKs) was investigated in rat pinealocytes. Treatment with dibutyryl cGMP (DBcGMP) dose-dependently increased the phosphorylation of both p44 and p42 isoforms of MAPK. This effect of DBcGMP was abolished by PD98059 (a MAPK kinase inhibitor), H7 (a nonspecific protein kinase inhibitor), and KT5823 [a selective cGMP-dependent protein kinase (PKG) inhibitor]. Elevation of cellular cGMP content by treatment with norepinephrine, zaprinast (a cGMP phosphodiesterase inhibitor), or nitroprusside was effective in activating MAPK. Natriuretic peptides that were effective in elevating cGMP levels in this tissue were also effective in activating MAPK. Our results indicate that, in this neuroendocrine tissue, the cGMP/PKG signaling pathway is an important mechanism used by hormones and neurotransmitters in activating MAPK.
Ho
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Department of Physiology, Faculty of Medicine, University of Alberta, Edmonton, Canada.
Hashimoto
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Chik
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D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002227:Carbazoles; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D007211:Indoles; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology; D020098:Natriuretic Peptide, C-Type / Q000494:pharmacology; D009490:Neurosecretory Systems / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D009599:Nitroprusside / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010766:Phosphorylation; D010870:Pineal Gland / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011688:Purinones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013439:Sulfhydryl Reagents / Q000494:pharmacology; D013449:Sulfonamides; D013873:Thionucleotides / Q000494:pharmacology
C090860:8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphorothioate; D000470:Alkaloids; D002227:Carbazoles; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007211:Indoles; D007546:Isoquinolines; D009281:Naphthalenes; D010726:Phosphodiesterase Inhibitors; D011688:Purinones; D013439:Sulfhydryl Reagents; D013449:Sulfonamides; D013873:Thionucleotides; C073601:KT 5823; D020098:Natriuretic Peptide, C-Type; D009599:Nitroprusside; D003995:Dibutyryl Cyclic GMP; D009320:Atrial Natriuretic Factor; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C011145:zaprinast; D006152:Cyclic GMP; C058819:calphostin C; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one