EFFECT OF A NEW V1 ANTAGONIST (OPC-21268) ON VASCULAR ACTION OF VASOPRESSIN IN CULTURED RAT VASCULAR SMOOTH-MUSCLE CELLS

The effect of 1-{1-[4-(3-acetylaminopropoxy)benzoyl]-4-piperidyl-3,4-dihydro-2(1H)-quinolinone} (OPC-21268) on vascular action of arginine vasopressin (AVP) was examined in cultured rat vascular smooth muscle cells (VSMC) by the measurement of cytosolic free calcium concentration ([Ca2+]i) and the AVP V1 receptor study. The preincubation of cells with OPC-21268 for 10 min inhibited the AVP-induced mobilization of [Ca2+]i in a dose-dependent manner but did not affect the angiotensin II-induced mobilization of [Ca2+]i. The receptor study revealed that OPC-21268 blocks the binding of AVP to the receptor in VSMC in a similar way to the V1 structural antagonist [1-(β-mercapto-β,β-cyclopentamethylenepropionic acid)-2-O-methyltyrosine]AVP: d(CH2)5Tyr(Me)AVP. Lineweaver-Burk plot showed that OPC-21268 is the competitive AVP V1 receptor antagonist. These results therefore indicate that OPC-21268 specifically blocks the vascular action of AVP mediated through the competitive inhibition of AVP binding to the receptors in VSMC. © 1991.