Phosphoinositide turnover signaling stimulated by ET-3 in endothelial cells from spontaneously hypertensive rats.
Endothelin (ET) B-type receptor-mediated signal transduction after stimulation with ET-3 was examined in cultured aortic endothelial cells obtained from spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. The purpose of this study was to elucidate ETB receptor-mediated response in endothelial cells from hypertensive rat models. Non-isopeptide-selective displacement and affinity in these binding experiments suggest that aortic endothelial cell receptors for ET-3 correspond to ETB receptor subtypes. These receptors for ET-3 were similar in WKY and SHR endothelial cells. ETB receptor mRNA expression in cultured endothelial cells was also similar in WKY and SHR. However, the cytosolic free Ca2+ level in the absence of extracellular Ca2+ as well as the inositol 1,4,5-trisphosphate level in response to ET-3 were greater in endothelial cells from SHR than in those from WKY. Phospholipase C and protein kinase C activities after stimulation with ET-3 were also greater in SHR than in WKY. The 6-ketoprostaglandin F1 alpha production was also augmented in SHR, although nitric oxide formation and guanosine 3',5'-cyclic monophosphate production after stimulation with ET-3 were similar in WKY and SHR. We conclude that the phosphoinositide turnover signaling stimulated by ET-3 is augmented in cultured aortic endothelial cells from SHR compared with those from WKY.
Yokokawa
K
K
First Department of Internal Medicine, Osaka City University Medical School, Japan.
Johnson
J
J
Kohno
M
M
Mandal
A K
AK
Yanagisawa
M
M
Horio
T
T
Yasunari
K
K
Takeda
T
T
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D016232:Endothelins / Q000494:pharmacology / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D011464:Epoprostenol / Q000096:biosynthesis; D006973:Hypertension / Q000378:metabolism*; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D009994:Osmolar Concentration; D010455:Peptides / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000378:metabolism
D016232:Endothelins; D010455:Peptides; D010716:Phosphatidylinositols; D015544:Inositol 1,4,5-Trisphosphate; D011464:Epoprostenol; D011493:Protein Kinase C; D010738:Type C Phospholipases; D002118:Calcium