Desensitization to PGEs was investigated in isolated longitudinal muscle strips of guinea-pig ileum in the presence of atropine /7.2xlo-7M/. Incubation with a conditioning dose of PGE2 /6.4xlo-7M/ for 5 min. resulted after washing out the drug in a clearcut reduction of sensitivity to a test dose of PGE2 /3.2xlo-7M/. This effect became more pronounced when conditioning was carried out with higher concentrations of PGE2 /3.2xlo-6 or 1.6xlo-5M/. Incubation with different doses of PGE1 /4xlo-6, 2xlo-5 or lo-4M/ exerted a similar effect on contractions due to the test dose of PGE2 /3.2xlo-7M/. This reduction in sensitivity proved to be specific for PGE2, as under similar conditions the action of histamine /4.7xlo-6M/ and BaCl2 /4.1xlo-4M/ was not reduced but even potentiated. The kinetics of recovery of sensitivity to PG were investigated applying every 4 min. the test dose of PGE2, until contractions approached control values. The time required for reaching 64% of control contraction height /T64/ was determined and a dose-effect relationship could be established between the conditioning dose of PGs and the T64 values. The dose-recovery lines for PGE1 and PGE2 proved to be parallel. On basis of these findings in the guinea-pig ileum the existence of a common receptor for PGE1 and PGE2 is suggested. The above facts may be explained as specific desensitization on this PG receptor site.
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