Endothelin-1-induced downregulation of ETB receptor mRNA: participation of cAMP.
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.
Asada
S
S
Department of Pharmacology, University of Tsukuba, Ibaraki, Japan.
Kasuya
Y
Y
Sakurai
T
T
Masaki
T
T
Goto
K
K
D000818:Animals; D001483:Base Sequence; D000242:Cyclic AMP / Q000502:physiology*; D015536:Down-Regulation; D016232:Endothelins / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D017466:Receptors, Endothelin / Q000187:drug effects* / Q000235:genetics; D014407:Tumor Cells, Cultured
D016232:Endothelins; D012333:RNA, Messenger; D017466:Receptors, Endothelin; D000242:Cyclic AMP