Desensitization of platelet-activating factor receptors, induced by inflammation in guinea pig ileal smooth muscle cells.
OBJECTIVE
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 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.


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.
Jeanneton
O
O
Department of Pharmacology, Institut National de la Recherche Agronomique, Toulouse, France.
Delvaux
M
M
Frexinos
J
J
Bueno
L
L
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002470:Cell Survival; D015232:Dinoprostone / Q000494:pharmacology; D004224:Diterpenes; D046934:Ginkgolides; D006168:Guinea Pigs; D007079:Ileitis / Q000503:physiopathology*; D007082:Ileum / Q000187:drug effects* / Q000502:physiology; D007213:Indomethacin / Q000494:pharmacology; D007783:Lactones / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D010972:Platelet Activating Factor / Q000494:pharmacology*; D010980:Platelet Membrane Glycoproteins / Q000187:drug effects / Q000502:physiology*; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D018078:Receptors, Prostaglandin E / Q000502:physiology; D014302:Trinitrobenzenesulfonic Acid
D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; 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; C045856:ginkgolide B; D015232:Dinoprostone; D000109:Acetylcholine; D007213:Indomethacin