ARGININE-VASOPRESSIN INDUCES CONTRACTION AND STIMULATES GROWTH OF CULTURED HUMAN HEPATIC STELLATE CELLS

Background gr Aims: Hepatic stellate cells (HSCs) are perisinusoidal c ells believed to participate in the regulation of hepatic blood flow b ecause of their contractile properties and presence of receptors for s everal vasoactive factors, It is unknown whether HSCs have receptors f or vasopressin, one of the most potent endogenous vasoconstrictors. Th is study investigated the existence of receptors for and the effects o f arginine vasopressin (AVP) on cultured human HSCs, Methods: Intracel lular calcium concentration ([Ca2+](i)) and cell contraction were meas ured in individual cells loaded with fura-2 using a morphometric metho d with an epifluorescence microscope coupled to a CCD imaging system ( Photometrics, Tucson, AZ), AVP-specific binding was measured with [H-3 ]AVP, Mitogen-activated protein kinase (MAPk) activity and DNA synthes is were measured by in vitro phosphorylation of myelin basic protein a nd [H-3]thymidine incorporation, respectively, Parallel experiments we re performed in vascular smooth muscle cells, Results: AVP elicited a dose-dependent increase in [Ca2+](i), and contraction of HSCs, Moreove r, AVP increased MAPk activity, DNA synthesis, and cell number, These effects were similar to those observed in vascular smooth muscle cells and were blocked by a V-1 receptor antagonist, The existence of V-1 r eceptors was further confirmed by binding studies, Conclusions: Human HSCs have V-1-vasopressin receptors that induce effects similar to tho se observed in vascular smooth muscle cells, AVP may play a role in th e regulation of HSC function.