The opioid specificity of beta-endorphin enhancement of murine lymphocyte proliferation.
Beta-endorphin (beta-end) is a potent analgesic peptide which exhibits a variety of pharmacological activities in the central nervous system (CNS) following binding of its N-terminus to specific opioid receptors. Although C-terminal binding sites for this 31-amino-acid peptide have been characterized in CNS tissue, identification of their possible function has been facilitated by studies of beta-end effects on lymphocyte activities. In this communication, we report a detailed analysis of the opioid specificity of the ability of beta-end to enhance T cell mitogen-induced proliferation in unfractionated murine splenocytes. Intact 31-amino-acid beta-end peptides from several species, including human, camel and rat, enhanced concanavalin A-stimulated [3H]thymidine uptake 50-640% in a dose-dependent, naloxone-irreversible fashion. The presence of the C-terminal amino acids was required for the enhancement activity, since met-enkephalin, alpha- and gamma-endorphin, and human beta-end 1-27 were ineffective. Accordingly, the truncated peptides, human beta-end 6-31 and 18-31, were also able to enhance the Con A response. However, human beta-end 18-31 was consistently not as effective as beta-end 6-31 or the intact 31-residue peptide. These data suggest that although the C-terminus contains the primary active sequence, the N-terminus contributes to the overall potency of the effect. In support of this assertion, N-acetylation, which abolishes opioid binding activity, resulted in a reduced magnitude of enhancement. The data suggest that beta-end interacts with a non-opioid receptor which has specificity characteristics strikingly similar to non-opioid receptors characterized in CNS tissue.
Gilmore
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Department of Neurology and Microbiology, USC School of Medicine, Los Angeles 90033.
Weiner
L P
LP
D000595:Amino Acid Sequence; D000818:Animals; D003208:Concanavalin A / Q000494:pharmacology; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009270:Naloxone / Q000494:pharmacology; D015213:Neuroimmunomodulation / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology; D011957:Receptors, Opioid / Q000187:drug effects / Q000276:immunology; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D001615:beta-Endorphin / Q000494:pharmacology*
D010446:Peptide Fragments; D011957:Receptors, Opioid; D003208:Concanavalin A; D009270:Naloxone; D001615:beta-Endorphin