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Platelet-activating factor-mediated vasoconstriction and glycogenolysis in the perfused rat liver
Journal article   Open access   Peer reviewed

Platelet-activating factor-mediated vasoconstriction and glycogenolysis in the perfused rat liver

Denis B Buxton, Rory A Fisher, Donald J Hanahan and Merle S Olson
The Journal of biological chemistry, Vol.261(2), pp.644-649
1986
DOI: 10.1016/S0021-9258(17)36141-0
PMID: 3001074
url
https://doi.org/10.1016/S0021-9258(17)36141-0View
Published (Version of record) Open Access

Abstract

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.
Fundamental and applied biological sciences. Psychology Biological and medical sciences Vertebrates: digestive system Liver. Bile. Biliary tracts

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