Correlation of desensitisation of platelet activating factor (PAF) receptors with intensity of inflammation and intestinal PAF content during experimental ileitis in guinea pig.
OBJECTIVE
To determine the kinetics of platelet activating factor (PAF) and prostaglandin E2 (PGE2) 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 PGE2 10 nM 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 PGE2 was progressively desensitised (2 logM rightward shift of its concentration-response curve: Cmax = 1 microM; p < 0.01). Between days 4 and 6, the concentration-response curve of PGE2 shifted by only 1 logM (p < 0.05) whereas the curve of PAF induced contraction shifted by 2 logM (Cmax = 1 microM; 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 PGE2 induced contractions were similar to those observed on day 1, and PAF content returned to basal.


CONCLUSIONS
Inflammation induced by TNB instillation triggers PAF and PGE2 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.
Jeanneton
O
O
INRA, Department of Pharmacology, Toulouse, France.
Delvaux
M
M
Langlois
Y
Y
Le Bars
P
P
Le Bars
J
J
Delisle
M B
MB
Frexinos
J
J
Bueno
L
L
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D048429:Cell Size / Q000187:drug effects; D002766:Cholecystokinin / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D007079:Ileitis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D007082:Ileum / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010972:Platelet Activating Factor / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*; D010980:Platelet Membrane Glycoproteins / Q000187:drug effects* / Q000378:metabolism; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D018078:Receptors, Prostaglandin E / Q000187:drug effects / Q000378:metabolism; D013268:Stimulation, Chemical; D013997:Time Factors; D014302:Trinitrobenzenesulfonic Acid
D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D018078:Receptors, Prostaglandin E; C039351:platelet activating factor receptor; D014302:Trinitrobenzenesulfonic Acid; D002766:Cholecystokinin; D015232:Dinoprostone; D000109:Acetylcholine