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Signaling through Delta Opioid Receptors on Murine Splenic T Cells and Stably Transfected Jurkat Cells
Author(s) -
SHARP BURT M.,
McKEAN DAVID J.,
McALLEN KATHY,
SHAHABI NAHID A.
Publication year - 1998
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1998.tb09580.x
Subject(s) - dadle , pertussis toxin , agonist , chemistry , calcium in biology , medicine , naltrindole , endocrinology , receptor , microbiology and biotechnology , g protein , biology , opioid receptor , biochemistry
A bstract : β‐Endorphin (β‐EP) and delta opoid receptor (DOR) agonists affect immune functions such as lymphocyte chemotaxis, proliferation, and cytokine production. Recent studies indicate that both neuronal DOR and novel G‐protein‐coupled receptors with high affinity for β‐EP and DOR agonists are expressed by mononuclear cells. In addition, proenkephalin A mRNA and enkephalin‐related peptides are expressed by lymphocytes. These investigations were conducted to identify signal transduction pathways that mediate the effects of β‐EP and DOR agonists on T cells. Calcium mobilization was studied because it is central to T‐cell activation initiated by antigen presentation to the T‐cell receptor (TCR). Using the calcium‐sensitive dye Fluo‐3 and flow cytofluorometry to determine the concentration of free intracellular calcium, physiological concentrations of β‐EP were shown to enhance concanvalin. A (con A)‐stimulated calcium mobilization by murine splenic T cells ( p < 0.01). The DOR antagonist, naltrindole, inhibited this, whereas CTAP, a selective mu OR antagonist, was ineffective. In addition, N‐Ac‐β‐EP and the μ OR agonist DAMGO, failed to mimic the effects of β‐EP. Although it was less potent than β‐EP, DADLE, a DOR agonist, also enhanced Con‐A‐induced calcium mobilization ( p < 0.01). A DOR‐transfected human T‐cell line (DOR‐Jul.1) was developed to study signal transduction. Both DADLE and the selective DOR agonist, deltorphin, rapidly increased intracellular free calcium concentrations; ED 50 s were 10 −9 M. Pertussis toxin prevented the response, and EGTA significantly reduced it. In addition, DADLE inhibited forskolin‐stimulated cAMP production (ED 50 : 10 −11 M). These findings with normal splenic T cells and DOR‐transfected T‐cell line indicate that β‐EP and DOR agonists affect calcium mobilization. This is likely to modulate downstream pathways that regulate T‐cell activation and function.