HOMOLOGOUS DESENSITIZATION OF PAF RECEPTORS VIA A PGE(2)-DEPENDENT PATHWAY ON INTESTINAL SMOOTH-MUSCLE

The aim of the present study was to evaluate the effect of in vitro pr eincubation with PAF of isolated smooth muscle cells from guinea pig i leum in order to assess possible PAF receptor desensitization. Cells d ispersed by enzymatic digestion were preincubated with PAF for 30 min and the contractile effect of PAF was then assayed. In cells preincuba ted for 30 min with 10 nM PAF, the concentration inducing maximal cell contraction was 1 mu M instead of 10 nM in freshly dispersed cells an d the EC(50) was 40 nM instead of 10 pM. This desensitization to the c ontractile effect of PAF was prevented when cells were preincubated fo r 30 min with PAF plus PAF antagonist BN52021, PGE(2) antagonist SC192 20, cyclooxygenase inhibitor indomethacin and the phospholipase A(2) i nhibitor bromophenacyl bromide. In similar experiments, no desensititi zation occurred for CCK8 receptors after preincubation with either PAF , PGE(2) or CCK8. These results indicate that homologous desensitizati on of PAF receptors could occur via a PGE(2)-dependent pathway in inte stinal smooth muscle cells from guinea pig.