12-hydroxy-5Z, 8Z, 10E, 14Z, eicosatetraenoic acid (12-HETE) stimulates cAMP production in normal human fibroblasts.
We report here that the 12-lipoxygenase metabolite of arachidonic acid, 12-hydroxy-5Z, 8Z, 10E, 14Z, eicosatetraenoic acid (12-HETE), stimulates cAMP production in human fibroblasts among various cultured cell lines tested. Although 12-HETE seemed to stimulate the phospholipase C (PLC)-protein kinase C (PKC) system, inhibitors against PLC and PKC did not reduce the cAMP production induced by 12-HETE, indicating that the activation of PLC-PKC system is not positively coupled with the stimulation of cAMP production. On the other hand, the cAMP production induced by 12-HETE was dependent on the Ca2+/calmodulin system in the cells. The results suggest that 12-HETE specifically stimulates Ca2+/calmodulin-dependent adenylyl cyclase to increase cAMP level in the fibroblasts.
Ueki
S
S
Department of Biological Sciences, Faculty of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan.
Takagi
J
J
Kobayashi
Y
Y
Sato
F
F
Saito
Y
Y
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005354:Fibrosarcoma; D018922:HL-60 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D013449:Sulfonamides / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D002614:Chelating Agents; D004791:Enzyme Inhibitors; D004963:Estrenes; D007211:Indoles; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D013449:Sulfonamides; D014665:Vasodilator Agents; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; C017967:W 7; C033772:N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide; D000242:Cyclic AMP; D015056:1-Methyl-3-isobutylxanthine; C064758:Ro 31-8220