Distinct inhibition by non-peptide and peptide arginine vasopressin antagonists of vasopressin-induced activation of mitogen-activated protein kinase in cultured rat vascular smooth muscle cells.
The preincubation of vascular smooth muscle cells (VSMC) with a non-peptide arginine vasopressin (AVP) antagonist (OPC-21268) (0.5 mM) for 10 min completely inhibited the 1 microM AVP-induced activation of mitogen-activated protein (MAP) kinase but did not affect the angiotensin II-, protein kinase C activator- or ionomycin-stimulated MAP kinase. Similar results were obtained with the simultaneous administration of AVP and OPC-21268. This inhibitory effect of OPC-21268 completely disappeared after washing the cells pretreated with OPC-21268. In contrast, the preincubation of VSMC with a peptide AVP antagonist, d(CH2)5Tyr(Me)AVP (1 microM), for 10 min completely blocked the 1 microM AVP-activated MAP kinase but the simultaneous administration of d(CH2)5Tyr(Me)AVP with AVP could inhibit that only by 40%. However, the washing procedure did not affect the inhibitory effect of d(CH2)5Tyr(Me)AVP. These results indicate that OPC-21268 is a specific AVP antagonist to inhibit the AVP-induced activation of MAP kinase. The antagonistic effect of OPC-21268 is also suggested to be relatively weak but prompt as compared to that of a peptide AVP antagonist d(CH2)5Tyr(Me)AVP.
Okada
K
K
Division of Endocrinology and Metabolism, Jichi Medical School, Tochigi, Japan.
Sasaki
R
R
Ishikawa
S
S
Saito
T
T
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D015759:Ionomycin / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology*; D010880:Piperidines / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D010880:Piperidines; D015363:Quinolones; D000804:Angiotensin II; D001127:Arginine Vasopressin; C068644:OPC 21268; D015759:Ionomycin; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D013755:Tetradecanoylphorbol Acetate