Location of platelet activating factor binding in rat liver

Area of Science:

• Pharmacology
• Hepatology
• Microcirculation

Background:

• Platelet-activating factor (PAF) analogues, like 1-O-[3H]octadecyl-2-acetyl-sn-glycero-3-phosphocholine ([3H]AGEPC), are investigated for their biological effects.
• Understanding the localization and mechanism of AGEPC action in the liver is crucial for its therapeutic potential.

Purpose of the Study:

• To investigate the specific binding sites of [3H]AGEPC in the liver microvasculature.
• To determine the role of intact liver vasculature in the biological response to AGEPC.

Main Methods:

• Autoradiography of liver tissue slices perfused with [3H]AGEPC.
• Competition assays using unlabeled AGEPC analogues and U.66985.
• Measurement of glucose release stimulated by AGEPC in perfused livers and isolated cells.
• Effect of bovine serum albumin on AGEPC binding and glucose release.

Main Results:

• [3H]AGEPC binding was localized to portal venules in anterograde perfusion and central venules in retrograde perfusion.
• The majority of AGEPC binding was found to be non-specific.
• AGEPC stimulated glucose release in perfused livers but not in isolated hepatocytes or liver slices.
• Bovine serum albumin inhibited AGEPC-stimulated glucose release and reduced label retention in portal sinusoidal cells.

Conclusions:

• Specific binding of [3H]AGEPC is restricted to the portal side of the liver microvasculature.
• The biological response to AGEPC, such as glucose release, necessitates an intact and perfused liver vasculature.
• Isolated liver cells do not exhibit a response to AGEPC, highlighting the importance of the vascular system for its action.