Reduced prostaglandin E2 (PGE2) receptors on atopic T lymphocytes.
We have recently demonstrated that atopic T lymphocytes have decreased sensitivity to prostaglandin E2 (PGE2). In order to determine whether this decreased sensitivity was reflected at the receptor level, we have employed a radioligand binding assay utilizing [3H]PGE2. We have demonstrated a single specific reversible binding site for [3H]PGE2 on normal T cells (N = 10) with a mean KD (+/-SD) of 32.2 (+/-25.0) nM, a binding capacity of 20.2 (+/-13.0) pM, and a mean of 1004 (+/-118) receptors per cell. Atopic T cells (N = 10) were also found to have a single specific binding site for [3H]PGE2 with a mean KD of 24.9 (+/-17.8) nM, a binding capacity of 7.1 (+/-10.1) pM, and a mean of 372 (+/-61) receptors per cell. These radioligand binding studies were correlated with functional studies in the same subjects. Phytohemagglutinin-stimulated protein synthesis ([3H]leucine uptake) was suppressed in a dose-dependent fashion by PGE2 (10(-6)-10(-12) M). The maximal effect of PGE2 on normal T cells was 10(-6) M PGE2 with an IC50 of 10(-12) M. Atopic T cells responded quantitatively less than normal T cells to PGE2. Further, the maximum suppression of protein synthesis by PGE2 occurred at 10(-6) M with an IC50 of 10(-10) to 10(-11) M. These studies suggest that part of the decreased sensitivity of atopic T cells to PGE2 may result from a reduction in PGE2 binding sites.
D003864:Depression, Chemical; D015232:Dinoprostone; D004351:Drug Resistance; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology*; D008213:Lymphocyte Activation; D011458:Prostaglandins E / Q000378:metabolism / Q000494:pharmacology*; D014176:Protein Biosynthesis; D011982:Receptors, Prostaglandin / Q000172:deficiency* / Q000378:metabolism; D018078:Receptors, Prostaglandin E; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism
D011458:Prostaglandins E; D011982:Receptors, Prostaglandin; D018078:Receptors, Prostaglandin E; D015232:Dinoprostone