Antagonism of platelet-activating factor in isolated rat colon: possible mechanism.

The contractions of three different regions of rat colon in response to platelet-activating factor (PAF) were compared. The ascending colon was found to be the most responsive. The slow contraction of the ascending colon induced by PAF was dependent on external Ca2+. CV-3988, a structural analog of PAF, slowly induced irreversible inhibition of PAF-induced contraction, whereas FR-900452, which is structurally unrelated to PAF, caused rapid reversible inhibition of PAF-induced contraction. No inhibitory effects of CV-3988 were observed when the strip was washed with Tyrode's solution containing 1% bovine serum albumin (BSA). The results suggest that PAF and CV-3988 penetrate slowly into the outer half of the lipid bilayer of plasma membranes of cells in isolated rat colon, and then rapidly diffuse laterally to associate firmly with specific binding sites.