Glucocorticoid amplifies vasopressin-induced phosphoinositide hydrolysis in aortic smooth muscle cells.
It has been reported that glucocorticoid modifies phosphoinositide (PI) hydrolysis stimulated by vasoactive agents in vascular smooth muscle cells. In the present study, we investigated the point at which glucocorticoid affects vasopressin-induced PI hydrolysis in primary cultured rat aortic smooth muscle cells. The pretreatment with dexamethasone significantly amplified the formation of inositol trisphosphate (IP3) induced by vasopressin in a dose-dependent manner in a range of 1 pM to 10 nM. The effect of dexamethasone was dependent on the time of pretreatment up to 8 h. Dexamethasone had little effect on the number of vasopressin receptor and its affinity to vasopressin. The pretreatment with dexamethasone also amplified the formation of IP3 induced by NaF, a GTP-binding protein activator, or angiotensin II. 12-O-Tetradecanoylphorbol-13-acetate, a protein kinase C (PKC)-activating phorbol ester, significantly reduced the dexamethasone-induced enhancement of IP3 formation stimulated by vasopressin, angiotensin II or NaF 4 alpha-Phorbol-12, 13-didecanoate, a PKC-nonactivating phorbol ester, had little effect on the enhancement by dexamethasone. These results strongly suggest that glucocorticoid amplifies vasopressin-induced PI hydrolysis at a point downstream from GTP-binding protein in primary cultured rat aortic smooth muscle cells, and that the activation of PKC has a negative feedback effect on the amplification by glucocorticoid of vasopressin-induced PI hydrolysis.
Watanabe
Y
Y
First Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Tokuda
H
H
Suzuki
A
A
Shinoda
J
J
Kotoyori
J
J
Ito
Y
Y
Oiso
Y
Y
Kozawa
O
O
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D004357:Drug Synergism; D004789:Enzyme Activation; D005246:Feedback; D006868:Hydrolysis; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D011493:Protein Kinase C / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014667:Vasopressins / Q000494:pharmacology*
D010716:Phosphatidylinositols; D014667:Vasopressins; D003907:Dexamethasone; D015544:Inositol 1,4,5-Trisphosphate; D011493:Protein Kinase C