Skip to main content
NCBI home page
Immunology logoLink to Immunology
. 1993 May;79(1):18–23.

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

P van den Bergh 1, J Rozing 1, L Nagelkerken 1
PMCID: PMC1422059  PMID: 8509139

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.

Full text

PDF
18

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Chen C. Y., Salles G., Seldin M. F., Kister A. E., Reinherz E. L., Shipp M. A. Murine common acute lymphoblastic leukemia antigen (CD10 neutral endopeptidase 24.11). Molecular characterization, chromosomal localization, and modeling of the active site. J Immunol. 1992 May 1;148(9):2817–2825. [PubMed] [Google Scholar]
  2. Gilman S. C., Schwartz J. M., Milner R. J., Bloom F. E., Feldman J. D. beta-Endorphin enhances lymphocyte proliferative responses. Proc Natl Acad Sci U S A. 1982 Jul;79(13):4226–4230. doi: 10.1073/pnas.79.13.4226. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Gilmore W., Weiner L. P. The opioid specificity of beta-endorphin enhancement of murine lymphocyte proliferation. Immunopharmacology. 1989 Jan-Feb;17(1):19–30. doi: 10.1016/0162-3109(89)90004-0. [DOI] [PubMed] [Google Scholar]
  4. Harbour D. V., Smith E. M., Blalock J. E. Splenic lymphocyte production of an endorphin during endotoxic shock. Brain Behav Immun. 1987 Jun;1(2):123–133. doi: 10.1016/0889-1591(87)90015-8. [DOI] [PubMed] [Google Scholar]
  5. Hazum E., Chang K. J., Cuatrecasas P. Specific nonopiate receptors for beta-endorphin. Science. 1979 Sep 7;205(4410):1033–1035. doi: 10.1126/science.224457. [DOI] [PubMed] [Google Scholar]
  6. Hemmick L. M., Bidlack J. M. Beta-endorphin stimulates rat T lymphocyte proliferation. J Neuroimmunol. 1990 Sep-Oct;29(1-3):239–248. doi: 10.1016/0165-5728(90)90167-l. [DOI] [PubMed] [Google Scholar]
  7. Kavelaars A., Ballieux R. E., Heijnen C. J. Differential effects of beta-endorphin on cAMP levels in human peripheral blood mononuclear cells. Brain Behav Immun. 1990 Sep;4(3):171–179. doi: 10.1016/0889-1591(90)90020-q. [DOI] [PubMed] [Google Scholar]
  8. Kavelaars A., Ballieux R. E., Heijnen C. J. In vitro beta-adrenergic stimulation of lymphocytes induces the release of immunoreactive beta-endorphin. Endocrinology. 1990 Jun;126(6):3028–3032. doi: 10.1210/endo-126-6-3028. [DOI] [PubMed] [Google Scholar]
  9. Lolait S. J., Clements J. A., Markwick A. J., Cheng C., McNally M., Smith A. I., Funder J. W. Pro-opiomelanocortin messenger ribonucleic acid and posttranslational processing of beta endorphin in spleen macrophages. J Clin Invest. 1986 Jun;77(6):1776–1779. doi: 10.1172/JCI112501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. McCain H. W., Lamster I. B., Bozzone J. M., Grbic J. T. Beta-endorphin modulates human immune activity via non-opiate receptor mechanisms. Life Sci. 1982 Oct 11;31(15):1619–1624. doi: 10.1016/0024-3205(82)90054-6. [DOI] [PubMed] [Google Scholar]
  11. Nagelkerken L., Henfling M., van Breda Vriesman P. Accessory cell function of thoracic duct nonlymphoid cells, dendritic cells, and splenic adherent cells in the Brown-Norway rat. Cell Immunol. 1985 Jul;93(2):520–531. doi: 10.1016/0008-8749(85)90156-x. [DOI] [PubMed] [Google Scholar]
  12. Norman D. C., Morley J. E., Chang M. P. Aging decreases beta-endorphin enhancement of T-cell mitogenesis in mice. Mech Ageing Dev. 1988 Aug;44(2):185–191. doi: 10.1016/0047-6374(88)90090-5. [DOI] [PubMed] [Google Scholar]
  13. Puppo F., Corsini G., Mangini P., Bottaro L., Barreca T. Influence of beta-endorphin on phytohemagglutinin-induced lymphocyte proliferation and on the expression of mononuclear cell surface antigens in vitro. Immunopharmacology. 1985 Oct;10(2):119–125. doi: 10.1016/0162-3109(85)90037-2. [DOI] [PubMed] [Google Scholar]
  14. Rosen H., Behar O., Abramsky O., Ovadia H. Regulated expression of proenkephalin A in normal lymphocytes. J Immunol. 1989 Dec 1;143(11):3703–3707. [PubMed] [Google Scholar]
  15. Schweigerer L., Schmidt W., Teschemacher H., Gramsch C. beta-Endorphin: surface binding and internalization in thymoma cells. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5751–5755. doi: 10.1073/pnas.82.17.5751. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Shahabi N. A., Linner K. M., Sharp B. M. Murine splenocytes express a naloxone-insensitive binding site for beta-endorphin. Endocrinology. 1990 Mar;126(3):1442–1448. doi: 10.1210/endo-126-3-1442. [DOI] [PubMed] [Google Scholar]
  17. Shahabi N. A., Peterson P. K., Sharp B. Beta-endorphin binding to naloxone-insensitive sites on a human mononuclear cell line (U937): effects of cations and guanosine triphosphate. Endocrinology. 1990 Jun;126(6):3006–3015. doi: 10.1210/endo-126-6-3006. [DOI] [PubMed] [Google Scholar]
  18. Shipp M. A., Stefano G. B., D'Adamio L., Switzer S. N., Howard F. D., Sinisterra J., Scharrer B., Reinherz E. L. Downregulation of enkephalin-mediated inflammatory responses by CD10/neutral endopeptidase 24.11. Nature. 1990 Sep 27;347(6291):394–396. doi: 10.1038/347394a0. [DOI] [PubMed] [Google Scholar]
  19. Sibinga N. E., Goldstein A. Opioid peptides and opioid receptors in cells of the immune system. Annu Rev Immunol. 1988;6:219–249. doi: 10.1146/annurev.iy.06.040188.001251. [DOI] [PubMed] [Google Scholar]
  20. Stein C., Hassan A. H., Przewłocki R., Gramsch C., Peter K., Herz A. Opioids from immunocytes interact with receptors on sensory nerves to inhibit nociception in inflammation. Proc Natl Acad Sci U S A. 1990 Aug;87(15):5935–5939. doi: 10.1073/pnas.87.15.5935. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Westly H. J., Kleiss A. J., Kelley K. W., Wong P. K., Yuen P. H. Newcastle disease virus-infected splenocytes express the proopiomelanocortin gene. J Exp Med. 1986 Jun 1;163(6):1589–1594. doi: 10.1084/jem.163.6.1589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Zurawski G., Benedik M., Kamb B. J., Abrams J. S., Zurawski S. M., Lee F. D. Activation of mouse T-helper cells induces abundant preproenkephalin mRNA synthesis. Science. 1986 May 9;232(4751):772–775. doi: 10.1126/science.2938259. [DOI] [PubMed] [Google Scholar]
  23. van den Bergh P., Rozing J., Nagelkerken L. Two opposing modes of action of beta-endorphin on lymphocyte function. Immunology. 1991 Apr;72(4):537–543. [PMC free article] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES