1. N-acetyl-beta-endorphin1-31 antagonizes the suppressive effect of beta-endorphin1-31 on murine splenocyte proliferation via a naloxone-resistant receptor.
- Author
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Shahabi NA, Burtness MZ, and Sharp BM
- Subjects
- Animals, Cells, Cultured, DNA Replication drug effects, Female, Kinetics, Lymphocyte Activation drug effects, Lymphocytes drug effects, Mice, Mice, Inbred Strains, Peptide Fragments antagonists & inhibitors, Phytohemagglutinins, Receptors, Opioid drug effects, Spleen, Thymidine metabolism, beta-Endorphin antagonists & inhibitors, Lymphocytes immunology, Naloxone pharmacology, Peptide Fragments pharmacology, Receptors, Opioid physiology, beta-Endorphin analogs & derivatives, beta-Endorphin pharmacology
- Abstract
High affinity binding sites for beta-endorphin1-31 (beta-EP) have been observed on transformed mononuclear cells such as the human U937 monocyte-like cell line and the murine EL4-thymoma line, and on normal murine splenocytes. Binding of beta-EP at these sites is resistant to competition by naloxone and other opiate receptor ligands but sensitive to N-acetyl-beta-endorphin1-31 (N-Ac), cations and GTP-gamma-sulfate. Thus, the following studies were done to determine the functional significance of binding beta-EP and N-Ac. beta-EP suppressed phytohemagglutinin (PHA)-stimulated [3H]thymidine uptake in a dose-dependent, naloxone-insensitive fashion. beta-Endorphin1-27, (des)-tyrosine beta-endorphin2-31, or N-Ac failed to duplicate the suppressive effect of beta-EP. However, N-Ac, which is equipotent to beta-EP at displacing 125I-beta-EP bound to murine splenocytes or U937 cells, antagonized the suppressive effect of beta-EP. Taken together with previous binding studies, the present observations suggest that beta-EP effects receptor-mediated responses on normal immunocytes that do not depend on the activation of neuronal-like opiate receptors which are naloxone-sensitive. N-Ac, which shows minimal binding to such brain opiate receptors, is a potent functional antagonist of the naloxone-insensitive immunocyte receptor for beta-EP.
- Published
- 1991
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