Platelet-activating factor-mediated vasoconstriction and glycogenolysis in the perfused rat liver.
Infusion of platelet-activating factor (alkyl acetylglycerophosphocholine (AGEPC] into isolated perfused rat livers caused a dose-dependent, transient increase in portal vein pressure, indicative of constriction of the hepatic vasculature. A close correlation was observed between the changes in portal pressure and concomitant transient increases in hepatic glucose output. The two processes displayed similar dose dependence and were attenuated to a similar extent by reducing the perfusate calcium concentration. Reducing the perfusate free calcium concentration to 1 nM by co-infusion of EGTA did not abolish completely the hepatic responses to AGEPC. Verapamil inhibited both the hemodynamic and glycogenolytic responses to AGEPC in a dose-dependent fashion; the IC50 was approximately 10 microM at an AGEPC concentration of 6.6 X 10(-11) M. Also, both responses displayed similar degrees of tachyphylaxis in response to repeated short infusions of AGEPC. Measurement of glycogen phosphorylase a in extracts from freeze-clamped livers demonstrated a rapid increase in phosphorylase a in response to infusion of AGEPC. A small but significant increase in whole tissue ADP was found in response to AGEPC (2 X 10(-8) M); cAMP levels were not changed by AGEPC infusion. It is concluded that glycogenolysis in the perfused liver in response to AGEPC may be a result of the hemodynamic effects of AGEPC, rather than a direct effect of the phospholipid mediator on the hepatocyte.
D000244:Adenosine Diphosphate / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D008112:Liver Glycogen / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011169:Portal Vein; D014661:Vasoconstriction / Q000187:drug effects*; D014690:Venous Pressure; D014700:Verapamil / Q000494:pharmacology
D008112:Liver Glycogen; D010972:Platelet Activating Factor; D000244:Adenosine Diphosphate; D014700:Verapamil; D000242:Cyclic AMP; D005947:Glucose; D002118:Calcium