Met-enkephalin-containing peptides encoded by proenkephalin A mRNA expressed in activated murine thymocytes inhibit thymocyte proliferation
| Autor: | K M, Linner, H E, Quist, B M, Sharp |
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| Rok vydání: | 1995 |
| Předmět: |
Mice
Inbred ICR Base Sequence Enkephalin Methionine Molecular Sequence Data Radioimmunoassay Antibodies Monoclonal Nucleic Acid Hybridization Enkephalins Thymus Gland Blotting Northern DNA Antisense Mice Receptors Opioid delta Concanavalin A Animals Female RNA Messenger Protein Precursors Oligopeptides Cell Division |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 154(10) |
| ISSN: | 0022-1767 |
| Popis: | 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 delta 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%. delta opioid receptor antagonists recognizing the delta-2 (naltrindole (NTI) and naltriben (NTB)), but not the delta-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 delta-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) delta 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 delta-2 subtype-specific antagonists, NTI and NTB, were functional and the delta-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 delta-2-like opioid receptors, and 2) these endogenous enkephalins function to inhibit the proliferation of activated thymocytes. |
| Databáze: | OpenAIRE |
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