Correlation of desensitisation of platelet activating factor (PAF) receptors with intensity of inflammation and intestinal PAF content during experimental ileitis in guinea pig

Aim - To determine the kinetics of platelet activating factor (PAF) and prostaglandin E-2 (PGE(2)) receptor desensitisation during intestinal inflammation induced by trinitrobenzenesulphonic acid (TNB) instillation and to study the relation between receptor regulation, inflammatory lesions, and PAF content of the gut wall. Methods - Receptor desensitisation was assessed on isolated smooth muscle cells from the circular layer. PAF content of the intestinal wall was determined by thin layer chromatography and radioimmunoassay. Results - After an acute inflammatory phase on day 1, subacute changes appeared in TNB instilled ileum, with a maximal intensity on day 6. In control animals, PAF 10 nM and PGE(2) 10 mM provoked a maximal contraction in the range of 24% of cell shortening. On days 1 and 3 after intestinal instillation of TNB, PAF induced contraction was not altered whereas the effect of PGE, was progressively desensitised (2 logM rightward shift of its concentration-response curve: C-max = 1 mu M; p < 0.01). Between days 4 and 6, the concentration-response curve of PGE, shifted by only 1 logM (p < 0.05) whereas the curve of PAF induced contraction shifted by 2 logM (C-max = 1 mu M; p < 0.01). The PAF content of the ileal wall was maximal between days 3 and 5 (300 ng/mg tissue). On days 10 and 15, PAF and PGE, induced contractions were similar to those observed on day 1, and PAF content returned to basal. Conclusion - Inflammation induced by TNB instillation triggers PAF and PGE, receptor desensitisation; this is dependent on the duration of inflammation and correlates with PAF content in the ileum. This receptor desensitisation may play a protective role by preventing overstimulation of intestinal smooth muscle cells.