CORRELATION OF DESENSITIZATION OF PLATELET-ACTIVATING-FACTOR (PAF) RECEPTORS WITH INTENSITY OF INFLAMMATION AND INTESTINAL PAF CONTENT DURING EXPERIMENTAL ILEITIS IN GUINEA-PIG
O. Jeanneton et al., CORRELATION OF DESENSITIZATION OF PLATELET-ACTIVATING-FACTOR (PAF) RECEPTORS WITH INTENSITY OF INFLAMMATION AND INTESTINAL PAF CONTENT DURING EXPERIMENTAL ILEITIS IN GUINEA-PIG, Gut, 43(3), 1998, pp. 356-364
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
.