Mesangial cells are centrally-located glomerular pericytes with contractile, endocrine, and immunity-regulating functions. These cells are thought to maintain normal glomerular function, since mesangial cell proliferation and extracellular matrix formation are hallmarks of chronic glomerular disease.
Vasopressin causes mesangial cell contraction, proliferation and
hypertrophy. Consequently, the effects of
YM218, a potent, nonpeptide
vasopressin V(1A) receptor-selective antagonist, on the growth responses of human mesangial cells to
vasopressin were investigated.
YM218 showed high affinity for
vasopressin V(1A) receptors, exhibiting a K(i) value of 0.18 nM.
Vasopressin concentration-dependently increased intracellular Ca(2+) levels and induced
hyperplasia and
hypertrophy in cultured mesangial cells,
YM218 potently inhibited these
vasopressin-induced responses. These results clearly show that
YM218 has both strong affinity for human mesangial cell
vasopressin V(1A) receptors and great potency in inhibiting the
vasopressin-induced growth responses of mesangial cells controlled by the
vasopressin V(1A) receptors. The
hyperplasia and
hypertrophy of mesangial cells in vitro caused by
vasopressin indicate its possible in vivo role in glomerular disease pathogenesis. Therefore,
YM218 is a potent pharmacologic probe to investigate the physiologic and pathophysiologic roles of
vasopressin in the development of renal disease.