Characteristics of Non-opioid β-Endorphin Receptor

Abstract

Tritium-labeled selective agonist of non-opioid beta-endorphin receptor, the decapeptide immunorphine ([3H]SLTCLVKGFY) with specific activity of 24 Ci/mmol has been prepared. By its use, non-opioid beta-endorphin receptors were revealed and characterized on mouse peritoneal macrophages and rat myocardium, spleen, adrenal, and brain membranes. The non-opioid beta-endorphin receptor of macrophages has in addition to immunorphine (Kd of the [3H]immunorphine-receptor complex was 2.4 +/- 0.1 nM) and beta-endorphin (Ki of the [3H]immunorphine specific binding was 2.9 +/- 0.2 nM) a high affinity for Fc-fragment of human IgG1, pentarphine (VKGFY), cyclopentarphine [cyclo(VKGFY)], and [Pro3]pentarphine (VKPFY) (Ki values were 0.0060 +/- 0.0004, 2.7 +/- 0.2, 2.6 +/- 0.2, and 2.8 +/- 0.2 nM, respectively) and is insensitive to naloxone and [Met5]enkephalin (Ki > 100 microM). Treatment of macrophages with trypsin resulted in the loss of their ability for the specific binding of [3H]immunorphine. Values of the specific binding of 8.4 nM [3H]immunorphine to rat adrenal, spleen, myocardium, and brain membranes were determined to be 1146.0 +/- 44.7, 698.6 +/- 28.1, 279.1 +/- 15.4, and 172.2 +/- 1.8 fmol/mg protein, respectively. Unlabeled beta-endorphin, pentarphine, [Pro3]pentarphine, cyclopentarphine, cyclodipentarphine [cyclo(VKGFYVKGFY)], and Fc-fragment of IgG1 inhibited the binding of [3H]immunorphine to membranes from these organs. No specific binding of [3H]immunorphine to rat liver, lung, kidney, and intestine membranes was found.

Role of β-endorphin in the regulation of proinflammatory cytokine production by peripheral blood monocytes in vitro

“…High-affinity naloxone-insensitive receptor for BE is expressed on T lymphocytes, macrophages, adrenals, and nerve cells [3]. The effect of combined treatment with agonists and antagonists can be also realized via the interaction between opioids and various domains of the peptide chain within one receptor [8].…”

Evaluation of the Effect of β-Endorphin on IL-4 and γ-IFN Production by CD4+ Lymphocytes

“…Virtually all populations of immune cells serve as the targets for β-endorphin. The presence of opioid receptors of the three main classes (µ, δ, κ) and nonopioid receptor on their surface was proven by the radioligand binding method and detection of the corresponding RNA [2,6,8]. β-Endorphin modulates proliferation of lymphocytes and production of IL-2, IL-4 and γ-IFN [1,10].…”

Negative inotropic and chronotropic effects of δ-opioid receptor antagonists are mediated via non-opioid receptors

“…The data obtained cannot exclude the possibility that δ-ligands interact with so-called nonopioid receptors for opioid peptides [5,9]. The existence of non-opioid receptors for dynorphin in cardiomyocytes is demonstrated [9].…”

“…produce effects opposite to that of agonists) [7]. However, it is not clear whether δ-antagonists produce similar effect on isolated perfused heart, and how they affect the heart in vivo [2].Opioid peptides were shown to interact with socalled "non-opioid receptors of opioid peptides" [1,5,9]. There are no similar data on the interaction of OR antagonists with non-opioid receptors, but this phenomenon cannot be excluded.…”