Desensitization of platelet-activating factor receptors, induced by inflammation in guinea pig ileal smooth muscle cells |
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Authors: | Oliver Jeanneton Michel Delvaux Jacques Frexinos Lionel Bueno |
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Institution: | ∗Department of Pharmacology, Institut National de la Recherche Agronomique, Toulouse, France;‡Laboratory of Digestive Motility, CHU Rangueil, Toulouse, France |
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Abstract: | 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). 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. In cells from saline-treated animals, PAF induced a maximal cell contraction at 10 nmol/L and half-maximal contraction (EC50) was 9 ± 0.2 pmol/L. After TNB injection, the maximal contraction induced by PAF was observed at 1000 nmol/L and EC50 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. 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. |
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Keywords: | Abbreviations: CMax concentration inducing maximal contraction EC50 half-maximal contraction IC50 half-maximal inhibition PAF platelet-activating factor TNB trinitrobenzenesulfonic acid |
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