CORRELATION OF DESENSITIZATION 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) an d prostaglandin E-2 (PGE(2)) receptor desensitisation during intestina l inflammation induced by trinitrobenzenesulphonic acid (TNB) instilla tion and to study the relation between receptor regulation, inflammato ry lesions, and PAF content of the gut wall. Methods - Receptor desens itisation was assessed on isolated smooth muscle cells from the circul ar layer. PAF content of the intestinal wall was determined by thin la yer chromatography and radioimmunoassay. Results - After an acute infl ammatory phase on day 1, subacute changes appeared in TNB instilled il eum, 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, w as progressively desensitised (2 logM rightward shift of its concentra tion-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 maxima l 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 T NB instillation triggers PAF and PGE, receptor desensitisation; this i s dependent on the duration of inflammation and correlates with PAF co ntent in the ileum. This receptor desensitisation may play a protectiv e role by preventing overstimulation of intestinal smooth muscle cells .