The C-terminal tetrapeptide of beta-endorphin (MPF) enhances lymphocyte proliferative responses

Abstract

Human MPF (Lys-Lys-Gly-Glu) stimulates the proliferative response of human lymphocytes to the T-cell mitogen concanavalin A by 121-751% in the concentration range 10(-11)-10(-4) M; the peak effect is at 10(-8) M, lower or higher concentrations eliciting reduced responses, i.e. the dose-response curve is bell-shaped. Species specificity is high. Human MPF similarly stimulates rat lymphocytes, but the peak effect is seen at a 100-fold higher dose (10(-6) M). Rat MPF (Lys-Lys-Gly-Gln) has a peak effect at 10(-6) M with human lymphocytes, but the peak effect with rat lymphocytes is at a 1000-fold lower dose (10(-9) M). Truncated forms of the MPFs (Gly-Glu, Gly-Gln, Gly, Glu, Gln) and opioid peptides (beta-endorphin, [Leu] and [Met]enkephalin) show insignificant or only weak stimulatory or inhibitory effects. These results suggest that MPF acts via specific non-opioid receptors located on lymphocytes and that endogenously released MPF may have an important role in the functioning of the immune system.