Enhanced phosphoinositide turnover signalling stimulated by endothelin B-type receptor in endothelial cells from spontaneously hypertensive rats.
1. Endothelin (ET) B-type (ETB) receptor-mediated signal transduction was examined after stimulation with ET-3 in cultured aortic endothelial cells (EC) from spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats (8 weeks old). 2. The EC from both rat strains expressed only ETB receptor mRNA. The receptor densities and affinities, which were non-selective for ET-1, -2, -3 and Sarafotoxin S6c, and mRNA expression were similar in WKY and SHR. 3. The cytosolic Ca2+ level in the absence of extracellular Ca2+, inositol 1,4,5-trisphosphate levels, protein kinase C and phospholipase C activities in response to ET-3 were greater in SHR EC than in WKY EC. 4. The 45Ca uptake in response to ET-3, which was blocked by Ni2+, was smaller in SHR EC than in WKY EC. 5. The 6-keto-PGF1alpha production was augmented in SHR, though nitric oxide formation after stimulation with ET-3 was similar. 6. These results suggest that ETB receptor-mediated phosphoinositide turnover signalling is augmented in SHR EC through postreceptor mechanism.
Yokokawa
K
K
First Deparment of Internal Medicine, Osaka City University Medical School, Japan.
Kohno
M
M
Minami
M
M
Ikeda
M
M
Horio
T
T
Kano
H
H
Hanehira
T
T
Yasunari
K
K
Takeda
T
T
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D065128:Endothelin Receptor Antagonists; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D066298:In Vitro Techniques; D010716:Phosphatidylinositols / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017466:Receptors, Endothelin / Q000096:biosynthesis / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D065128:Endothelin Receptor Antagonists; D010716:Phosphatidylinositols; D012333:RNA, Messenger; D017466:Receptors, Endothelin; D015121:6-Ketoprostaglandin F1 alpha; D002118:Calcium