부산대학교 도서관

Vasopressin (AVP) causes mesangial cell contraction, proliferation and hypertrophy. The present study investigated the effects of YM218, a potent, nonpeptide AVP V1A receptor-selective antagonist, on rat mesangial cells using binding, signal transduction and cell growth assays. Specific binding of 3H-AVP to rat mesangial cell plasma membranes was dependent upon time, temperature and membrane protein concentration. Scatchard plot analysis of equilibrium binding data revealed the existence of a single class of high-affinity binding sites with the expected V1A receptor profile. YM218 showed high affinity for V1A receptors, exhibiting a Ki value of 0.19 nmol/l. AVP concentration-dependently increased intracellular Ca2+ ([Ca2+]i) levels, stimulated mitogen-activated protein (MAP) kinase and induced hyperplasia. Conversely, YM218 potently suppressed [Ca2+]i elevation, activation of MAP kinase and hyperplasia induced by AVP. These results indicate that YM218 displays both high affinity for rat mesangial cell V1A receptors and high potency in inhibiting AVP-induced signal transduction and growth response. Therefore, YM218 is a useful pharmacologic tool for investigating the physiologic and pathophysiologic roles of AVP in kidney, and may have clinical application in the prevention or regression of mesangial cell growth. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]