β-Endorphin-like Peptide SLTCLVKGFY Is a Selective Agonist of Nonopioid β-Endorphin Receptor

Opioids As Modulators of Cell Death and Survival—Unraveling Mechanisms and Revealing New Indications

“…Cell proliferation in spleen and bone marrow was also increased in -opioid receptor knockout mice (Tian et al, 1997). However, in contrast to these immunosuppressive effects, ␤-endorphin increased the number of natural killer cells in the spleen (Kowalski, 1997), enhanced conditioned NK cell activity (Mandler et al, 1986;Hsueh et al, 1995) and concanavalin A-induced proliferation (van den Bergh et al, 1991;Navolotskaya et al, 2002b), IL-2 production (van den Bergh et al, 1991), and Ca 2ϩ mobilization in T-cells (Shahabi et al, 1996). The latter effect was shared by Met-enkephalin and inhibited with the DOR-specific antagonist naltrindole (Shahabi et al, 1996), indicating that this effect was probably mediated through the ␦ receptor.…”

Binding of synthetic peptide TPLVTLFK to nonopioid beta‐endorphin receptor on rat brain membranes

“…An artificial peptide (14 amino acid residues) corresponding to the β‐endorphin‐like IgG sequence has been synthesized and found to interact with rat brain receptors for β‐endorphin4. We synthesized the decapeptide SLTCLVKGFY (immunorphin) that competes with 125 I‐labeled β‐endorphin for binding to naloxone‐insensitive binding sites on human and mouse immunocompetent cells5–9 as well as on rat brain membranes12. At present β‐endorphin is known to interact with immunocompetent cells via not only opioid, but also nonopioid (naloxone‐insensitive) receptor mechanisms.…”

“…We have synthesized the decapeptide SLTCLVKGFY corresponding to the amino acid sequence 364–373 of the heavy chain of human IgG of subclasses 1–4 (referred to as immunorphin)5 and found that it is a selective agonist of nonopioid (insensitive to naloxone) β‐endorphin receptor of human T‐lymphocytes6–9, mouse peritoneal macrophages10, 11, synaptic membranes of rat brain12, rat adrenal cortex membranes13, 14, and human Jurkat lymphoblastic T‐cells15. The investigations of biological activity of immunorphin showed that it increases the Con A‐induced proliferation of human T‐lymphocytes in vitro 6–9, activates mouse peritoneal macrophages in vitro and in vivo 10, 11, stimulates the growth of human lymphoblast T‐cell lines Jurkat and MT‐415, 16, inhibits the adenylate cyclase activity in rat adrenocortical membranes and the secretion of corticosterone from the adrenal glands to the bloodstream13, and stimulates cell division in early mouse blastocysts in vitro 17, 18. Study of the distribution of the nonopioid receptor of β‐endorphin in the body of the rat showed that it is present on the cells of the immune (macrophages and lymphocytes), nervous (synaptic membranes of the brain), and cardiovascular systems (myocardium membranes)19.…”

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“…Only in 1996, when the decapeptide immunorphin SLTCLVKGFY corresponding to sequence364-373 of the human IgG(1-4) heavy chain was synthesized ( Figure 1) and it was found that it is aselective agonist of the nonopioid β-endorphin receptor, the relationship between all these facts became obvious [10]. It turned out that immunorphin labeled with iodine-125 or tritium is capable of binding with high affinity to human T lymphocytes, murine peritoneal macrophages, synaptic membranes of the rat brain, and the cells of the human T-lymphoblast line Jurkat, its binding in all cases being insensitive to naloxone [11][12][13][14][15][16][17]. IgG(1-4) heavy chain [7].…”

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The review presents data on nonopioid action of β-endorphin and its synthetic fragment [12][13][14][15][16][17][18][19] octarphin), a selective agonist of a nonopioid β-endorphin receptor. Using tritium labeled octarphin, the receptor distribution in the body has been studied.

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