DESENSITIZATION OF PLATELET-ACTIVATING-FACTOR RECEPTORS, INDUCED BY INFLAMMATION IN GUINEA-PIG ILEAL SMOOTH-MUSCLE CELLS

Background/Aims: Platelet-activating factor (PAF) is involved in the pathophysiology of motility changes induced by intestinal inflammation. The aim of this study was to evaluate a possible desensitization of PAF receptors in guinea pig intestinal smooth muscle cells after experimental inflammation induced by trinitrobenzenesulfonic acid (TNB). Methods: Saline or TNB (80 mg/kg) was injected in the intestinal lumen, and the animals were killed 6 days later. Smooth muscle cells from the circular layer were isolated, and cell contraction induced by PAF was measured. Results: In cells from saline-treated animals, PAF induced a maximal cell contraction at 10 nmoI/L and half-maximal contraction (EC(50)) was 9 +/- 0.2 pmol/L. After TNB injection, the maximal contraction induced by PAF was observed at 1000 nmol/L and ECS, was 300 +/- 70 pmol/L, indicating a 2 logmol/L right shift of the concentration-response curve of PAF. When animals were treated with the PAF antagonist, 20 mg/kg BN52021, or with 2 mg/kg indomethacin for the 6 days after TNB instillation, the right-sided shift of the concentration-response curve of PAF did not occur. Conclusions: Desensitization of PAF receptors occurring in intestinal smooth muscle cells after TNB instillation could be mediated in vivo by PAF itself via a prostaglandin-dependent pathway.