Beta-endorphin modulates T-cell intracellular calcium flux and c-myc expression via a potassium channel.
To characterize the effect of beta-endorphin on T-lymphocyte activation, we examined its influence on membrane currents, intracellular calcium flux, and c-myc mRNA levels during mitogenic stimulation of Jurkat cells. While beta-endorphin weakly enhanced voltage-activated K+ currents of Jurkat cells by itself, it suppressed these currents in the presence of mitogen. Naloxone, by itself, also enhanced K+ current amplitude, but in the presence of mitogen partially reversed the suppressive effect of beta-endorphin. A 5-30 min exposure to beta-endorphin resulted in an increase in the rate of mitogen-stimulated intracellular calcium release and an increase in c-myc mRNA levels relative to controls. Longer exposure (1-2 h) to beta-endorphin retarded intracellular calcium release, and suppressed c-myc expression. The suppressive effects were reversed by naloxone and mimicked by the K+ channel blocker, tetraethylammonium ion. These data suggest that opiate receptors and K+ channels of Jurkat cells are functionally coupled in a way that modulates intracellular calcium release and c-myc expression - two key processes in T-cell mitogenesis.
Hough
C J
CJ
Laboratory of Biochemical Genetics, NIMH, Neuroscience Center, St. Elizabeths, Washington, DC 20032.
Halperin
J I
JI
Mazorow
D L
DL
Yeandle
S L
SL
Millar
D B
DB
D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D008564:Membrane Potentials; D009270:Naloxone / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D001615:beta-Endorphin / Q000494:pharmacology*
D015221:Potassium Channels; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D013757:Tetraethylammonium Compounds; D009270:Naloxone; D001615:beta-Endorphin; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium