J. Biol. Chem., Vol. 261, Issue 2, 644-649, 01, 1986
Platelet-activating factor-mediated vasoconstriction and glycogenolysis in the perfused rat liver
DB Buxton, RA Fisher, DJ Hanahan and MS Olson
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.