Homologous desensitization of PAF receptors via a PGE2-dependent pathway on intestinal smooth muscle.
The aim of the present study was to evaluate the effect of in vitro preincubation with PAF of isolated smooth muscle cells from guinea pig ileum in order to assess possible PAF receptor desensitization. Cells dispersed by enzymatic digestion were preincubated with PAF for 30 min and the contractile effect of PAF was then assayed. In cells preincubated for 30 min with 10 nM PAF, the concentration inducing maximal cell contraction was 1 microM instead of 10 nM in freshly dispersed cells and the EC50 was 40 nM instead of 10 pM. This desensitization to the contractile effect of PAF was prevented when cells were preincubated for 30 min with PAF plus PAF antagonist BN52021, PGE2 antagonist SC19220, cyclooxygenase inhibitor indomethacin and the phospholipase A2 inhibitor bromophenacyl bromide. In similar experiments, no desensitization occurred for CCK8 receptors after preincubation with either PAF, PGE2 or CCK8. These results indicate that homologous desensitization of PAF receptors could occur via a PGE2-dependent pathway in intestinal smooth muscle cells from guinea pig.
Jeanneton
O
O
Department of Pharmacology, INRA, Toulouse, France.
Delvaux
M
M
Botella
A
A
Frexinos
J
J
Bueno
L
L
D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D015232:Dinoprostone / Q000494:pharmacology / Q000502:physiology*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure*; D010972:Platelet Activating Factor / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000187:drug effects / Q000502:physiology*; D011453:Prostaglandins / Q000096:biosynthesis; D011956:Receptors, Cell Surface; D011949:Receptors, Cholecystokinin / Q000187:drug effects / Q000502:physiology; D043562:Receptors, G-Protein-Coupled; D018078:Receptors, Prostaglandin E / Q000187:drug effects / Q000502:physiology; D012680:Sensitivity and Specificity; D012844:Sincalide / Q000494:pharmacology; D013997:Time Factors
D000098:Acetophenones; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011453:Prostaglandins; D011956:Receptors, Cell Surface; D011949:Receptors, Cholecystokinin; D043562:Receptors, G-Protein-Coupled; D018078:Receptors, Prostaglandin E; C039351:platelet activating factor receptor; D015232:Dinoprostone; D012844:Sincalide; C006821:4-bromophenacyl bromide; D007213:Indomethacin