Stimulation of human peripheral lymphocytes by methionine enkephalin and delta-selective opioid analogues.
The opioid peptide methionine enkephalin was shown to stimulate human peripheral lymphocyte proliferation in vitro in the absence of mitogen. A study of the time course of stimulation revealed a maximum proliferative response, measured by [3H]thymidine incorporation, after 4-5 days incubation. The kinetics of the response are similar to those for in vitro T cell responses to antigen rather than via polyclonal activation through lectin or anti-CD3 triggering, suggesting a physiological basis for the phenomenon. The stimulatory influence was blocked by the delta-selective antagonist ICI-174864, suggesting the mediation of classical opioid delta receptors. The opioid receptor specificity is further demonstrated using delta- and mu-selective agonists. The delta-selective agonists DSLET and DPDPE stimulate proliferation, whereas the mu-selective agonist DAGON was without effect.
Hucklebridge
F H
FH
Polytechic of Central London, School of Biological and Health Sciences, London, U.K.
Hudspith
B N
BN
Lydyard
P M
PM
Brostoff
J
J
D000328:Adult; D004723:Endorphins / Q000494:pharmacology*; D020881:Enkephalin, D-Penicillamine (2,5)-; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004744:Enkephalin, Methionine / Q000494:pharmacology*; D004745:Enkephalins / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009292:Narcotic Antagonists / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D011957:Receptors, Opioid / Q000187:drug effects / Q000276:immunology; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu
D004723:Endorphins; D004745:Enkephalins; D009292:Narcotic Antagonists; D009842:Oligopeptides; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D004744:Enkephalin, Methionine; D004743:Enkephalin, Leucine; C034318:enkephalin, Ser(2), Leu(5), Thr(6)-; D020881:Enkephalin, D-Penicillamine (2,5)-; C040643:N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine