Met-enkephalin-containing peptides encoded by proenkephalin A mRNA expressed in activated murine thymocytes inhibit thymocyte proliferation

K. M. Linner, H. E. Quist, Burt Sharp

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

Murine thymocytes activated with the mitogen Con A express proenkephalin A mRNA (PEA mRNA) and met-enkephalin and/or met-enkephalin-containing peptides ('enkephalins'). This Con A-induced expression of PEA mRNA is modulated by the δ opioid receptor agonist, deltorphin I, in a biphasic, dose-dependent manner. That is, 10-13 M to 10-11 M deltorphin enhanced PEA mRNA expression 3- to 3.5-fold over the level induced by Con A alone, and 10-9 M to 10-7 M deltorphin inhibited it 40 to 70%. δ opioid receptor antagonists recognizing the δ-2 (naltrindole (NTI) and naltriben (NTB)), but not the δ- 1 (7-benzylidenenaltrexone (BNTX)), subtype of opioid receptor described in brain, reversed both the enhancing and inhibiting effects of deltorphin on Con A-induced PEA mRNA expression. In addition, the δ-2 receptor-specific antagonists, NTI and NTB, directly inhibited Con A-induced PEA mRNA expression. The function of the enkephalins expressed by thymocytes was examined by using 1) δ opioid receptor antagonists, 2) PEA mRNA-specific antisense cDNA, and 3) Ab to met-enkephalin, and measuring cell proliferation. All three reagents caused enhancement of Con A-induced proliferation, with effects ranging from two- to fourfold over the response to Con A alone. Again, the δ-2 subtype-specific antagonists, NTI anti NTB, were functional and the δ-1 subtype-specific antagonist, BNTX, was not. The PEA mRNA-specific antisense cDNA blocked translation but not transcription of PEA mRNA. The data suggest that 1) endogenous enkephalins induced in thymocytes modulate their own expression through δ-2-like opioid receptors, and 2) these endogenous enkephalins function to inhibit the proliferation of activated thymocytes.

Original languageEnglish (US)
Pages (from-to)5049-5060
Number of pages12
JournalJournal of Immunology
Volume154
Issue number10
StatePublished - 1995

Fingerprint

Methionine Enkephalin
Thymocytes
naltrindole
Messenger RNA
Peptides
Enkephalins
Opioid Receptors
Narcotic Antagonists
Complementary DNA
proenkephalin
Mitogens
Cell Proliferation
Brain

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

Met-enkephalin-containing peptides encoded by proenkephalin A mRNA expressed in activated murine thymocytes inhibit thymocyte proliferation. / Linner, K. M.; Quist, H. E.; Sharp, Burt.

In: Journal of Immunology, Vol. 154, No. 10, 1995, p. 5049-5060.

Research output: Contribution to journalArticle

@article{026ab673b15b475d9c40c058182bd2da,
title = "Met-enkephalin-containing peptides encoded by proenkephalin A mRNA expressed in activated murine thymocytes inhibit thymocyte proliferation",
abstract = "Murine thymocytes activated with the mitogen Con A express proenkephalin A mRNA (PEA mRNA) and met-enkephalin and/or met-enkephalin-containing peptides ('enkephalins'). This Con A-induced expression of PEA mRNA is modulated by the δ opioid receptor agonist, deltorphin I, in a biphasic, dose-dependent manner. That is, 10-13 M to 10-11 M deltorphin enhanced PEA mRNA expression 3- to 3.5-fold over the level induced by Con A alone, and 10-9 M to 10-7 M deltorphin inhibited it 40 to 70{\%}. δ opioid receptor antagonists recognizing the δ-2 (naltrindole (NTI) and naltriben (NTB)), but not the δ- 1 (7-benzylidenenaltrexone (BNTX)), subtype of opioid receptor described in brain, reversed both the enhancing and inhibiting effects of deltorphin on Con A-induced PEA mRNA expression. In addition, the δ-2 receptor-specific antagonists, NTI and NTB, directly inhibited Con A-induced PEA mRNA expression. The function of the enkephalins expressed by thymocytes was examined by using 1) δ opioid receptor antagonists, 2) PEA mRNA-specific antisense cDNA, and 3) Ab to met-enkephalin, and measuring cell proliferation. All three reagents caused enhancement of Con A-induced proliferation, with effects ranging from two- to fourfold over the response to Con A alone. Again, the δ-2 subtype-specific antagonists, NTI anti NTB, were functional and the δ-1 subtype-specific antagonist, BNTX, was not. The PEA mRNA-specific antisense cDNA blocked translation but not transcription of PEA mRNA. The data suggest that 1) endogenous enkephalins induced in thymocytes modulate their own expression through δ-2-like opioid receptors, and 2) these endogenous enkephalins function to inhibit the proliferation of activated thymocytes.",
author = "Linner, {K. M.} and Quist, {H. E.} and Burt Sharp",
year = "1995",
language = "English (US)",
volume = "154",
pages = "5049--5060",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "10",

}

TY - JOUR

T1 - Met-enkephalin-containing peptides encoded by proenkephalin A mRNA expressed in activated murine thymocytes inhibit thymocyte proliferation

AU - Linner, K. M.

AU - Quist, H. E.

AU - Sharp, Burt

PY - 1995

Y1 - 1995

N2 - Murine thymocytes activated with the mitogen Con A express proenkephalin A mRNA (PEA mRNA) and met-enkephalin and/or met-enkephalin-containing peptides ('enkephalins'). This Con A-induced expression of PEA mRNA is modulated by the δ opioid receptor agonist, deltorphin I, in a biphasic, dose-dependent manner. That is, 10-13 M to 10-11 M deltorphin enhanced PEA mRNA expression 3- to 3.5-fold over the level induced by Con A alone, and 10-9 M to 10-7 M deltorphin inhibited it 40 to 70%. δ opioid receptor antagonists recognizing the δ-2 (naltrindole (NTI) and naltriben (NTB)), but not the δ- 1 (7-benzylidenenaltrexone (BNTX)), subtype of opioid receptor described in brain, reversed both the enhancing and inhibiting effects of deltorphin on Con A-induced PEA mRNA expression. In addition, the δ-2 receptor-specific antagonists, NTI and NTB, directly inhibited Con A-induced PEA mRNA expression. The function of the enkephalins expressed by thymocytes was examined by using 1) δ opioid receptor antagonists, 2) PEA mRNA-specific antisense cDNA, and 3) Ab to met-enkephalin, and measuring cell proliferation. All three reagents caused enhancement of Con A-induced proliferation, with effects ranging from two- to fourfold over the response to Con A alone. Again, the δ-2 subtype-specific antagonists, NTI anti NTB, were functional and the δ-1 subtype-specific antagonist, BNTX, was not. The PEA mRNA-specific antisense cDNA blocked translation but not transcription of PEA mRNA. The data suggest that 1) endogenous enkephalins induced in thymocytes modulate their own expression through δ-2-like opioid receptors, and 2) these endogenous enkephalins function to inhibit the proliferation of activated thymocytes.

AB - Murine thymocytes activated with the mitogen Con A express proenkephalin A mRNA (PEA mRNA) and met-enkephalin and/or met-enkephalin-containing peptides ('enkephalins'). This Con A-induced expression of PEA mRNA is modulated by the δ opioid receptor agonist, deltorphin I, in a biphasic, dose-dependent manner. That is, 10-13 M to 10-11 M deltorphin enhanced PEA mRNA expression 3- to 3.5-fold over the level induced by Con A alone, and 10-9 M to 10-7 M deltorphin inhibited it 40 to 70%. δ opioid receptor antagonists recognizing the δ-2 (naltrindole (NTI) and naltriben (NTB)), but not the δ- 1 (7-benzylidenenaltrexone (BNTX)), subtype of opioid receptor described in brain, reversed both the enhancing and inhibiting effects of deltorphin on Con A-induced PEA mRNA expression. In addition, the δ-2 receptor-specific antagonists, NTI and NTB, directly inhibited Con A-induced PEA mRNA expression. The function of the enkephalins expressed by thymocytes was examined by using 1) δ opioid receptor antagonists, 2) PEA mRNA-specific antisense cDNA, and 3) Ab to met-enkephalin, and measuring cell proliferation. All three reagents caused enhancement of Con A-induced proliferation, with effects ranging from two- to fourfold over the response to Con A alone. Again, the δ-2 subtype-specific antagonists, NTI anti NTB, were functional and the δ-1 subtype-specific antagonist, BNTX, was not. The PEA mRNA-specific antisense cDNA blocked translation but not transcription of PEA mRNA. The data suggest that 1) endogenous enkephalins induced in thymocytes modulate their own expression through δ-2-like opioid receptors, and 2) these endogenous enkephalins function to inhibit the proliferation of activated thymocytes.

UR - http://www.scopus.com/inward/record.url?scp=0029018765&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029018765&partnerID=8YFLogxK

M3 - Article

C2 - 7730611

AN - SCOPUS:0029018765

VL - 154

SP - 5049

EP - 5060

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 10

ER -