Identification of two moieties of beta-endorphin with opposing effects on rat T-cell proliferation.

Abstract

In a previous study we demonstrated that beta-endorphin (beta-end) may stimulate rat T-cell proliferation via triggering of non-opioid receptors, whereas this stimulatory effect is abrogated by interaction of beta-end with opioid receptors. In the present study we provide evidence for this dualistic nature of beta-end by the identification of stimulatory and inhibitory sites of beta-end with the use of peptide fragments. The fragments beta-end6-31 and beta-end 18-31, which both lack the opioid receptor binding N-terminal sequence, enhanced rat T-cell proliferation when added directly to the cultures. By contrast, the peptide fragments beta-end24-31 and beta-end28-31 did not stimulate proliferation. Peptides and fragments containing the N-terminal part, i.e. methionine-enkephalin (met-enk), alpha-endorphin (alpha-end), gamma-endorphin, the fragment beta-end1-27, and the intact beta-end, did not influence proliferation by themselves. However, the addition of met-enk or alpha-end to T cells that had been stimulated by the fragments beta-end6-31 or beta-end18-31 resulted in the abrogation of the stimulating effect. These data further support the hypothesis that beta-end is a peptide with a dualistic nature: its C-terminal moiety enhances T-cell proliferation, whereas this stimulatory effect can be prevented by peptides that possess the N-terminal enkephalin sequence.