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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Sharp, B. M. Mcallen, K. Heagy, W. Mckean, D. J. Shahabi, N. A. Huntoon, C. Bell, M. |
| Description | Author Affiliation: Sharp BM ( Endocrine-Neuroscience Research Laboratory, Minneapolis Medical Research Foundation, MN, USA.); |
| Abstract | Opiates are known to function as immunomodulators, in part by effects on T cells. However, the signal transduction pathways mediating the effects of opiates on T cells are largely undefined. To determine whether pathways that regulate free intracellular calcium ([Ca2+]i) and/or cAMP are affected by opiates acting through delta-type opioid receptors (DORs), a cDNA encoding the neuronal DOR was expressed in a stably transfected Jurkat T-cell line. The DOR agonists, deltorphin and [D-Ala2, D-Leu5]-enkephalin (DADLE), elevated [Ca2+]i, measured by flow cytofluorometry using the calcium-sensitive dye, Fluo-3. At concentrations from 10(-11)-10(-7) M, both agonists increased [Ca2+]i from 60 nM to peak concentrations of 400 nM in a dose-dependent manner within 30 sec (ED50 of approximately 5 x 10(-9) M). Naltrindole, a selective DOR antagonist, abolished the increase in [Ca2+]i, and pretreatment with pertussis toxin was also effective. To assess the role of extracellular calcium, cells were pretreated with EGTA, which reduced the initial deltorphin-induced elevation of [Ca2+]i by more than 50% and eliminated the second phase of calcium mobilization. Additionally, the effect of DADLE on forskolin-stimulated cAMP production was determined. DADLE reduced cAMP production by 70% (IC50 of approximately equal to 10(-11) M), and pertussis toxin inhibited the action of DADLE. Thus, the DOR expressed by a transfected Jurkat T-cell line is positively coupled to pathways leading to calcium mobilization and negatively coupled to adenylate cyclase. These studies identify two pertussis toxin-sensitive, G protein-mediated signaling pathways through which DOR agonists regulate the levels of intracellular messengers that modulate T-cell activation. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 16 |
| Volume Number | 93 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 1996-09-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Receptors, Opioid, Delta Physiology T-Lymphocytes Adenylate Cyclase Toxin Calcium Chelating Agents Pharmacology Colforsin Cyclic AMP Egtazic Acid Enkephalin, Leucine-2-Alanine GTP-Binding Proteins Oligopeptides Pertussis Toxin Signal Transduction Transfection Virulence Factors, Bordetella Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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