Delta-opioid receptor antagonist inhibits immunomodulation by Met-enkephalin analogs.
The methionine-enkephalin (Met-enkephalin, Tyr-Gly- Gly-Phe-Met) analogs Tyr-D-Ala-Gly-MePhe-Met NHC(3)H(7)-iso (1) and Tyr-D-Ala-Gly-MePhe-Gly-NHC(3)H(7)-iso (2) have been shown to enhance human T cell proliferation in in vitro treatment. Their immunomodulatory activities were completely blocked by naloxone, an opioid antagonist. Now we demonstrate that a selective delta-opioid receptor antagonist, ICI-174,864, completely blocks enhancement of T cell proliferation by analogs (1) and (2). The T cell-stimulatory effect was only partially inhibited by the mu-receptor-selective antagonist, beta-funaltrexamine hydrochloride. The kappa-opioid receptor antagonist, nor-binaltorphimine dihydrochloride, showed no effect on T cell-proliferation stimulated by analogs (1) and (2). These observations suggest that analogs (1) and (2) of Met-enkephalin stimulate T cell proliferation predominantly via delta-opioid receptor present on T cells.
Singh
V K
VK
Department of Immunology, Sanjay Gandhi Post-Graduate Institute of Medical Sciences, Lucknow, India. vksingh@sgpgi.ac.in
Bajpai
K
K
Narayan
P
P
Yadav
V S
VS
Dhawan
V C
VC
Haq
W
W
Mathur
K B
KB
Agarwal
S S
SS
D000276:Adjuvants, Immunologic; D002455:Cell Division / Q000187:drug effects; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors*; D013601:T-Lymphocytes / Q000187:drug effects
D000276:Adjuvants, Immunologic; D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; C051844:norbinaltorphimine; D004744:Enkephalin, Methionine; D004743:Enkephalin, Leucine; D009271:Naltrexone; C024524:beta-funaltrexamine; C040643:N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine