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. A lthough 12-HETE seemed to stimulate the phospholipase C (PLC)-protein kinas e C (PKC) system, inhibitors against PLC and PKC did not reduce the cAMP pr oduction induced by 12-HETE, indicating that the activation of PLC-PKC syst em is not positively coupled with the stimulation of cAMP production. On th e other hand, the cAMP production induced by 12-HETE was dependent on the C a2+/calmodulin system in the cells. The results suggest that 12-HETE specif ically stimulates Ca2+/calmodulin-dependent adenylyl cyclase to increase cA MP level in the fibroblasts. (C) 1999 Wiley-Liss, Inc.