N-acetyl-beta-endorphin1-31 antagonizes the suppressive effect of beta-endorphin1-31 on murine splenocyte proliferation via a naloxone-resistant receptor.
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.
Shahabi
N A
NA
Department of Medicine, Hennepin County Medical Center, Minneapolis, MN.
Burtness
M Z
MZ
Sharp
B M
BM
D000818:Animals; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects; D005260:Female; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D009270:Naloxone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010835:Phytohemagglutinins; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D013154:Spleen; D013936:Thymidine / Q000378:metabolism; D001615:beta-Endorphin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D010446:Peptide Fragments; D010835:Phytohemagglutinins; D011957:Receptors, Opioid; D009270:Naloxone; D001615:beta-Endorphin; C035101:N-acetyl-beta-endorphin; D013936:Thymidine