Effects of met-enkephalin on cell proliferation in different models of adrenocortical-cell growth

  • Authors:
    • Ludwik K. Malendowicz
    • Piera Rebuffat
    • Cinzia Tortorella
    • Gastone G. Nussdorfer
    • Agnieszka Ziolkowska
    • Anna Hochol
  • View Affiliations

  • Published online on: May 1, 2005     https://doi.org/10.3892/ijmm.15.5.841
  • Pages: 841-845
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Abstract

Met-enkephalin (met-Enk) is an opioid peptide that acts via three main subtypes of receptors referred to as μ (mu)-, δ (delta)- and ζ (zeta)-receptor. While the first two receptor subtypes mediate the classic opioid effects of met-Enk, ζ-receptors are reported to be involved in the non-opioid actions of the peptide, i.e. the inhibitory effect on the cell growth. Despite the fact that met-Enk is known to regulate the function of the hypothalamic-pituitary-adrenal axis acting on both its central and peripheral branches, none is known on the effects of met-Enk on adrenal growth. Hence, we have investigated the effects of met-Enk and its receptor agonists and antagonists on cell proliferation in three different models of rat adrenal growth: i) immature adrenal cortex, ii) regenerating adrenal cortex and iii) primary cultures of adrenocortical cells. In in vivo experiments, rats were given subcutaneous injections of 1 nmol/100 g of the peptides 28, 16 and 4 h before the sacrifice, and proliferative activity was assessed by counting the number of metaphase-arrested cells (after vincristine administration). In in vitro studies, cultured adrenocortical cells were exposed for 48 h to the peptides at a concentration of 10-6 M, and proliferative activity was measured by the EZ4U method. The blockade of μ- and δ-receptors raised proliferative activity in immature adrenals and decreased it in regenerating glands, and the effects were reversed by μ- and δ-receptor agonists. Naltrexone-induced blockade of all met-Enk receptor subtypes decreased proliferative activity in immature adrenal and raised it in regenerating glands. The exposure to either μ- or δ-receptor agonists and antagonists evoked doubtful or no effects on the proliferative activity of cultured adrenocortical cells. In contrast, met-Enk exerted a marked antiproliferogenic effect that was reversed by naltrexone. Taken together, these findings allow us to draw the following conclusions: i) μ- and δ-receptor activation inhibits the growth of immature adrenals, stimulates adrenal regeneration, and does not affect prolifer-ation of cultured adrenocortical cells; ii) ζ-receptors mediate the growth inhibitory effect of met-Enk on both regenerating adrenals and cultured adrenocortical cells, but unexpectedly their activation stimulates the growth of immature gland; and iii) the effects of μ- and δ-receptor activation in in vivo experiments are probably mediated by extra-adrenal indirect mechanisms.

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May 2005
Volume 15 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Malendowicz LK, Rebuffat P, Tortorella C, Nussdorfer GG, Ziolkowska A and Hochol A: Effects of met-enkephalin on cell proliferation in different models of adrenocortical-cell growth. Int J Mol Med 15: 841-845, 2005.
APA
Malendowicz, L.K., Rebuffat, P., Tortorella, C., Nussdorfer, G.G., Ziolkowska, A., & Hochol, A. (2005). Effects of met-enkephalin on cell proliferation in different models of adrenocortical-cell growth. International Journal of Molecular Medicine, 15, 841-845. https://doi.org/10.3892/ijmm.15.5.841
MLA
Malendowicz, L. K., Rebuffat, P., Tortorella, C., Nussdorfer, G. G., Ziolkowska, A., Hochol, A."Effects of met-enkephalin on cell proliferation in different models of adrenocortical-cell growth". International Journal of Molecular Medicine 15.5 (2005): 841-845.
Chicago
Malendowicz, L. K., Rebuffat, P., Tortorella, C., Nussdorfer, G. G., Ziolkowska, A., Hochol, A."Effects of met-enkephalin on cell proliferation in different models of adrenocortical-cell growth". International Journal of Molecular Medicine 15, no. 5 (2005): 841-845. https://doi.org/10.3892/ijmm.15.5.841