Location of platelet activating factor binding in rat liver.
Autoradiographs of tissue slices from livers perfused with 1 x 10(-9) M-1-O-[3H]octadecyl-2-acetyl-sn-glycero-3-phosphocholine ([ 3H]18:0-sn-3-AGEPC) indicate that binding of this agonist is localized in the portal venules in anterograde perfused livers, and in the central venules in retrograde perfused livers. The pattern of silver grains in anterograde perfused liver was not affected significantly by prior exposure to 100-fold excesses of unlabelled 16:0- or 18:0-sn-3-AGEPC, 16:0-sn-1-AGEPC, or a 1000-fold excess of U.66985. [3H]18:0-sn-3-lyso-GEPC produced the same pattern of binding as the acetylated analogue. Measurement of glucose release stimulated by 16:0-sn-3-AGEPC demonstrated that the retrograde perfused liver was nearly 1000-fold less sensitive to this compound than the anterograde perfused liver. Exposure of the livers to bovine serum albumin prior to 5 x 10(-11) M-[3H]18:0-sn-3-AGEPC resulted in inhibition of stimulated glucose release, and decreased both the amount of label retained in the livers and the amount of silver grains over the portal sinusoidal cells without affecting the amount of grains seen over all other regions of the liver. Glucose release from primary monolayer cultures of hepatocytes or suspensions of liver slices was not stimulated by 16:0-sn-3-AGEPC. The results suggest that specific binding of [3H]18:0-sn-3-AGEPC is restricted to the portal side of the liver microvasculature, the majority of binding is nonspecific, and the biological response to AGEPC requires an intact and perfused vasculature.
Hill
C E
CE
Department of Biochemistry, University of Texas Health Science Center, San Antonio 78284.
Miwa
M
M
Sheridan
P J
PJ
Hanahan
D J
DJ
Olson
M S
MS
D000818:Animals; D001345:Autoradiography; D002478:Cells, Cultured; D046508:Culture Techniques; D005947:Glucose / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D010656:Phenylephrine / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D012710:Serum Albumin, Bovine
D010972:Platelet Activating Factor; D010656:Phenylephrine; D012710:Serum Albumin, Bovine; D005947:Glucose