Receptor-mediated stimulation of taurocholate efflux from the rat hepatocyte and the ex vivo perfused rat liver.
The peptide hormone, arginine-vasopressin[( Arg8]vasopressin, AVP), stimulates efflux of the bile salts taurocholate and glycocholate from the rat hepatocyte in suspension via its association with the V1 receptor on the hepatic cell membrane. At a concentration ratio of 5:1 (antagonist to hormone), the V1 vasopressin antagonist, (dCH2)5Tyr(Me)AVP, inhibits the vasopressin induced efflux of taurocholate by approximately 82%, and of glycocholate, by approximately 85%. In contrast, the V2 antagonist (d(CH2)5[D-Ile2,Ala4]AVP, does not interfere with the stimulation of taurocholate and glycocholate efflux by vasopressin. In the isolated perfused rat liver, vasopressin (5 X 10(-10) M) causes an immediate increase of 55 +/- 12% over baseline in [14C]taurocholate secretion and a corresponding increase in bile flow. A more gradual and prolonged increase in [14C]taurocholate secretion, reflecting an increased biliary concentration of [14C]taurocholate, is observed beginning 6 min after vasopressin, reaching a plateau of 23 +/- 12% over baseline by 14 min and returning to baseline by 30 min. The mean rate of 14C secretion during the 30 min following administration of vasopressin (non-steady state) is increased by 14.3 +/- 6.4% over pre-infusion steady-state baseline (P less than 0.05). Prior administration of the V1 receptor antagonist d(CH2)5Tyr(Me)AVP attenuates these effects of vasopressin. The combination of these in vitro and in vivo findings suggest that vasopressin may play a role in regulating bile salt efflux. Furthermore, these studies in the isolated hepatocyte and the intact liver may provide a unique approach for defining biochemical changes associated with bile salt transport from the hepatic cell.
Kuhn
W F
WF
Department of Pharmacology, Medical College of Virginia, Richmond 23298.
Heuman
D M
DM
Vlahcevic
Z R
ZR
Gewirtz
D A
DA
D000818:Animals; D001127:Arginine Vasopressin / Q000037:antagonists & inhibitors / Q000378:metabolism; D001647:Bile Acids and Salts / Q000493:pharmacokinetics; D000001:Calcimycin / Q000493:pharmacokinetics; D002462:Cell Membrane / Q000648:ultrastructure; D006000:Glycocholic Acid / Q000493:pharmacokinetics; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D010716:Phosphatidylinositols / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000494:pharmacology*; D017483:Receptors, Vasopressin; D013656:Taurocholic Acid / Q000493:pharmacokinetics*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D001647:Bile Acids and Salts; D010716:Phosphatidylinositols; D011945:Receptors, Angiotensin; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D000001:Calcimycin; D013656:Taurocholic Acid; D006000:Glycocholic Acid; D013755:Tetradecanoylphorbol Acetate