Arginine vasopressin induces contraction and stimulates growth of cultured human hepatic stellate cells.
OBJECTIVE
Hepatic stellate cells (HSCs) are perisinusoidal cells believed to participate in the regulation of hepatic blood flow because of their contractile properties and presence of receptors for several vasoactive factors. It is unknown whether HSCs have receptors for vasopressin, one of the most potent endogenous vasoconstrictors. This study investigated the existence of receptors for and the effects of arginine vasopressin (AVP) on cultured human HSCs.


METHODS
intracellular calcium concentration ([Ca2+]i) and cell contraction were measured in individual cells loaded with fura-2 using a morphometric method with an epifluorescence microscope coupled to a CCD imaging system (Photometrics, Tucson, AZ). AVP-specific binding was measured with [3H]AVP. Mitogen-activated protein kinase (MAPk) activity and DNA synthesis were measured by in vitro phosphorylation of myelin basic protein and [3H]thymidine incorporation, respectively. Parallel experiments were performed in vascular smooth muscle cells.


RESULTS
AVP elicited a dose-dependent increase in [Ca2+]i and contraction of HSCs. Moreover, 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 V1 receptor antagonist. The existence of V1 receptors was further confirmed by binding studies.


CONCLUSIONS
Human HSCs have V1-vasopressin receptors that induce effects similar to those observed in vascular smooth muscle cells. AVP may play a role in the regulation of HSC function.
Bataller
R
R
Liver Unit, Hospital Clínic i Provincial, University of Barcelona School of Medicine, Catalunya, Spain.
Nicolás
J M
JM
Ginès
P
P
Esteve
A
A
Nieves Görbig
M
M
Garcia-Ramallo
E
E
Pinzani
M
M
Ros
J
J
Jiménez
W
W
Thomas
A P
AP
Arroyo
V
V
Rodés
J
J
D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D002118:Calcium / Q000032:analysis / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000032:analysis / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008099:Liver / Q000737:chemistry / Q000166:cytology* / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D051381:Rats; D017483:Receptors, Vasopressin / Q000032:analysis / Q000378:metabolism / Q000502:physiology; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D017483:Receptors, Vasopressin; D014316:Tritium; D001127:Arginine Vasopressin; D004247:DNA; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium; D013936:Thymidine