Asada S, Kasuya Y, Sakurai T, Masaki T, Goto K
Department of Pharmacology, University of Tsukuba, Ibaraki, Japan.
J Cardiovasc Pharmacol. 1995;26 Suppl 3:S272-5.
In this study we examined the participation of cAMP formation in endothelin-1 (ET-1)-induced downregulation of ETB receptor mRNA in ROS 17/2 rat osteosarcoma cells. Dibutyryl cAMP induced downregulation of ETB receptor mRNA in a time-dependent manner. ET-1 induced production of inositol phosphates and an increase of cAMP level in ROS 17/2 cells. A stimulatory effect on cAMP level was also observed when A23187 plus PMA was added to the cells. The increase in cAMP level induced either by ET-1 or by A23187 plus PMA was inhibited by indomethacin. The downregulation of ETB receptor mRNA induced by ET-1 was significantly inhibited by indomethacin. These results suggest that the ET-1-induced downregulation of ETB receptor mRNA in ROS 17/2 cells may be partly mediated through the increase in cAMP level secondary to the activation of the phosphoinositide hydrolysis/Ca2+ transduction cascade.
