Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the ability of selective opioid agonists and antagonists to influence pro-opiomelanocortin peptide secretion from the rat neurointermediate lobe in vitro. The mu-opioid agonist DAMGO ([D-Ala(2), N-Me-Phe(4), Gly(5)-ol]enkephalin) significantly stimulated beta-endorphin and alpha-melanocyte-stimulating hormone release relative to controls early (30 min) in the incubation period. Similar effects on beta-endorphin secretion were observed with the selective mu-opioid agonist dermorphin. The delta-opioid receptor agonist DPDPE ([D-Pen(2,5)]enkephalin) weakly inhibited beta-endorphin secretion relative to controls while the kappa-opioid receptor agonist U50488 had no effect. The mu-opioid selective antagonist CTOP (D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH(2)) inhibited basal beta-endorphin secretion while kappa- and delta-opioid receptor antagonists had no effect. Our data support a role for local mu-opioid receptor control of intermediate lobe pro-opiomelanocortin peptide secretion. Peptide secretion from melanotropes appears to be tonically stimulated by activation of mu-opioid receptors in the absence of intact neuronal innervation to the intermediate lobe.
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PMID:Mu and delta opioid receptor regulation of pro-opiomelanocortin peptide secretion from the rat neurointermediate pituitary in vitro. 1068 72

We have previously demonstrated that both endomorphin-1 and endomorphin-2 produce their antinociception by the stimulation of mu-opioid receptors. However, the antinociception induced by endomorphin-2 contains an additional component, which is mediated by the release of dynorphin A (1-17) acting on kappa-opioid receptors. These studies were done to determine whether the antinociception induced by endomorphin-1 and endomorphin-2 given supraspinally was mediated by the activation of different descending pain control pathways in the mouse. Specific receptor antagonists or antisera against endogenous opioid peptides were injected intrathecally to block the receptors or bind the released endogenous opioid peptides, and endomorphin-1 or endomorphin-2 was then administered i.c.v. to activate the descending pain control systems to produce antinociception. The tail-flick response was used as antinociceptive test. The blockade of the alpha(2)-adrenoceptors and 5-hydroxytryptamine receptors in the spinal cord by i.t. injection of yohimbine and methysergide, respectively, inhibited the antinociception induced by i.c.v.-administered endomorphin-1 and endomorphin-2. However, the antinociception induced by endomorphin-2 was inhibited by i.t. pretreatment with delta(2)-opioid receptor antagonist naltriben or kappa-opioid receptor antagonist nor-binaltorphimine, but not by the mu-opioid receptor antagonist D-Phe-Cys-Tyr-D-Try-Orn-Thr-Pen-Thr-NH(2) or the delta(1)-opioid receptor antagonist 7-benzylidene naltrexamine. Intrathecal pretreatment with antiserum against Met-enkephalin attenuated the antinociception induced by i.c.v.-administered endomorphin-2, but not endomorphin-1. Furthermore, i.t. pretreatment with antiserum against dynorphin A (1-17) also inhibited the antinociception induced by i.c.v.-administered endomorphin-2, but not endomorphin-1. Intrathecal pretreatment with antiserum against Leu-enkephalin or beta-endorphin did not inhibit i.c.v.-administered endomorphin-1- or endomorphin-2-induced antinociception. The results indicate that, like other opioid micro-receptor agonists, morphine, and [D-Ala(2), N-Me-Phe(4), Gly(5)-ol]-enkephalin, endomorphin-1 and endomorphin-2 given i.c.v. produce antinociception by activating spinipetal noradrenergic and serotonergic pathways for producing antinociception. However, the antinociception induced by endomorphin-2 given i.c.v. also contains other components, which are mediated by the release of Met-enkephalin and dynorphin A (1-17) acting on opioid delta(2)- and kappa-receptors, respectively, in the spinal cord.
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PMID:Differential mechanisms mediating descending pain controls for antinociception induced by supraspinally administered endomorphin-1 and endomorphin-2 in the mouse. 1094 66

We have previously demonstrated that the antinociception induced by either endomorphin-1 or endomorphin-2 given supraspinally is mediated by the stimulation of mu-opioid receptors. However, the antinociception induced by endomorphin-2 given supraspinally contains additional components, which are mediated by the spinal release of dynorphin A (1-17) acting on kappa-opioid receptors and the spinal release of [Met5]enkephalin acting on delta2-opioid receptors in the spinal cord. The present studies were performed to determine whether there are any differential effects on the tail-flick inhibition induced by endomorphin-1 and endomorphin-2 given intrathecally (i.t.) in mice. Endomorphin-1 or endomorphin-2 given i.t. inhibited the tail-flick response in a dose-dependent manner. The tail-flick inhibition induced by endomorphin-1 was blocked by i.t. pretreatment with mu-opioid receptor antagonist D-Phe-Cys-Tyr-D-Try-Orn-Thr-Pen-Thr-NH2 (CTOP), but not kappa-opioid receptor antagonist nor-binaltorphimine (nor-BNI), delta1-opioid receptor antagonist 7-benzylidene naltrexamine (BNTX), or delta2-opioid receptor antagonist naltriben (NTB). In contrast, the tail-flick inhibition induced by endomorphin-2 given i.t. was blocked by i.t. pretreatment with CTOP or nor-BNI, but not BNTX or NTB. Intrathecal pretreatment with antiserum against dynorphin A (1-17), but not antiserum against [Met5]enkephalin, [Leu5]enkephalin, or beta-endorphin, blocked the tail-flick inhibition induced by i.t.-administered endomorphin-2. None of these antisera attenuated the i.t.-administered endomorphin-1-induced tail-flick inhibition. It is concluded that the tail-flick inhibition induced by endomorphin-1 and endomorphin-2 given spinally is mediated by the stimulation of mu-opioid receptors. However, the tail-flick inhibition induced by spinally injected endomorphin-2 contains an additional component, which is mediated by the spinal release of dynorphin A (1-17) acting on kappa-opioid receptors in the spinal cord. We propose that there are at least two different subtypes of micro-opioid receptors for endomorphin-1 and endomorphin-2 to produce antinociception in the spinal cord.
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PMID:Differential antinociception induced by spinally administered endomorphin-1 and endomorphin-2 in the mouse. 1145 20

The mu-opioid receptor (MOR), a G-protein-coupled receptor, is internalized after endogenous agonist binding. Although receptor activation and internalization are separate events, internalization is a good assay for activation because endogenous opioid peptides all induce internalization. Estrogen treatment of ovariectomized rats induces MOR internalization, providing a neurochemical signature of estrogen activation of the medial preoptic nucleus. MOR activation appears to be the mechanism via which estrogen acts in the medial preoptic area to prevent the display of female reproductive behavior during the first 20-24 hr after estrogen treatment. Naltrexone, an alkaloid universal opioid receptor antagonist, prevented MOR internalization, suggesting that estrogen induces the release of endogenous opioid peptides that in turn activate the MOR. Enkephalins and beta-endorphin are nonselective endogenous MOR ligands. The most selective endogenous MOR ligands are the endomorphins. Infusions of selective MOR agonists, H-Tyr-d-Ala-Gly-N-Met-Phe-glycinol-enkephalin (DAMGO) or endomorphin-1, into the medial preoptic nucleus attenuated lordosis, and their effects were blocked with the MOR antagonist H-d-Phe-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr-NH(2) (CTOP). Infusion of endomorphin-1 internalized MOR. To determine whether progestin also acts via the MOR system to facilitate reproductive behavior, ovariectomized rats were primed with 17beta-estradiol and progesterone. Progestin facilitation of lordosis was correlated with a reduction of estrogen-induced MOR internalization. Progestin reversed estrogen-induced MOR internalization, suggesting that progesterone blocked estrogen-induced endogenous opioid release, relieving estrogen inhibition and facilitating lordosis. These results indicate a central role of MOR in the mediation of sex steroid activation of the CNS to regulate female reproductive behavior.
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PMID:Progesterone blockade of estrogen activation of mu-opioid receptors regulates reproductive behavior. 1146 44

The synthetic decapeptide H-SLTCLVKGFY-OH (termed immunorphin) corresponding to the sequence 364-373 of the CH3 domain of human immunoglobulin G heavy chain was found to compete with [125I]beta-endorphin for high-affinity receptors on T lymphocytes from the blood of healthy donors (K(i) = 0.6 nM). Besides immunorphin, its synthetic fragments H-Val-Lys-Gly-Phe-Tyr-OH (K(i) = 15 nM), H-Leu-Val-Lys-Gly-Phe-Tyr-OH (K(i) = 8.0 nM), H-Cys-Leu-Val-Lys-Gly-Phe-Tyr-OH (K(i) = 3.4 nM), H-Thr-Cys-Leu-Val-Lys-Gly-Phe-Tyr-OH (K(i) = 2.2 nM), H-Leu-Thr-Cys-Leu-Val-Lys-Gly-Phe-Tyr-OH (K(i) = 1.0 nM) possessed the ability to inhibit specific binding of [125I]beta-endorphin to T lymphocytes. Tests of the specificity of the receptors revealed that they are not sensitive to naloxone and Met-enkephalin, i.e. they are not opioid receptors. K(d) values characterizing the specific binding of 125I- labeled immunorphin and its fragment H-Val-Lys-Gly-Phe-Tyr-OH to the receptors have been determined to be 7.4 nM and 36.3 nM, respectively.
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PMID:Synthetic beta-endorphin-like peptide immunorphin binds to non-opioid receptors for beta-endorphin on T lymphocytes. 1178 84

Roles of endogenous opioid peptides and their receptors in modulation of the nocifensive responses to formalin in mice were studied. Mice were pretreated i.c.v. or intrathecally (i.t.) with selective opioid receptor antagonists or intrathecally with antisera against endogenous opioid peptides and the nocifensive licking responses to intraplantar injection of formalin (0.5%, 25 microl) were then observed. Pretreatment with the epsilon-opioid receptor antagonist beta-endorphin(1-27) or the selective mu-opioid receptor antagonist D-Phe-Cys-Tyr-Orn-Thr-Pen-Thr-NH(2) (CTOP) given i.c.v. dose dependently enhanced the second, but not the first phase of the nocifensive response. However, i.c.v. pretreatment with the selective delta-receptor antagonist naltrindole or kappa-receptor antagonist nor-binaltrophimine did not affect the nocifensive responses. Intrathecal pretreatment with selective delta(1)-opioid antagonist 7-benzylidene naltrexamine significantly enhanced both the first and second phases of nocifension. Intrathecal pretreatment with CTOP also increased the second but not the first phase of the nocifension. However, i.t. pretreatment with the selective delta(2)-receptor antagonist naltriben or nor-binaltrophimine did not affect the second phase of the nocifension. Intrathecal pretreatment with antiserum against Leu-enkephalin, Met-enkephalin, or dynorphin A(1-17), but not beta-endorphin, enhanced only the second phase of nocifensive response to formalin. It is concluded that the blockade of epsilon- and mu-receptors, but not delta- or kappa-receptors, at the supraspinal sites enhanced the second phase of formalin-induced nocifension. In the spinal cord, Leu-enkephalin, and to a lesser extent, Met-enkephalin and dynorphin A(1-17) and mu- and delta(1)-opioid receptors, but not delta(2)- or kappa-opioid receptors, are involved in modulating the feedback inhibition of the second phase of formalin-induced nocifension.
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PMID:Roles of endogenous opioid peptides in modulation of nocifensive response to formalin. 1180 28

It has been found that beta-endorphin (beta-END) and a synthetic beta-END-like decapeptide Ser-Leu-Thr-Cys-Leu-Val-Lys-Gly-Phe-Tyr (termed immunorphin, IMN) corresponding to the sequence 364-373 of human IgG heavy chain stimulate Con A-induced proliferation of T lymphocytes from the blood of healthy donors. [Met(5)]enkephalin ([Met(5)]ENK) and an antagonist of opioid receptors naloxone (NAL) tested in parallel were not active. The stimulating effect of beta-END and IMN on T lymphocyte proliferation was not inhibited by NAL. Studies on receptor binding of (125)I-labeled IMN to T lymphocytes revealed that it binds with high affinity to NAL-insensitive binding sites (K(d) = 7.0 +/- 0.3 nM). Unlabeled beta-END completely inhibited the specific binding of (125)I-labeled IMN to NAL-insensitive binding sites on T lymphocytes (K(i) = 1.1 +/- 0.2 nM). Thus, beta-END and IMN bind to common NAL-insensitive binding sites on T lymphocytes and enhance Con A-induced proliferation of these cells.
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PMID:beta-Endorphin-like peptide SLTCLVKGFY is a selective agonist of nonopioid beta-endorphin receptor. 1194 84

Beta-endorphin and the synthetic beta-endorphin-like decapeptide Ser-Leu-Thr-Cys-Leu-Val-Lys-Gly-Phe-Tyr (referred to as immunorphin), corresponding to the sequence 364-373 of the CH3 domain of human immunoglobulin G heavy chain, were shown to stimulate concanavalin A-induced proliferation of T lymphocytes from the blood of healthy donors. [Met(5)]Enkephalin and the antagonist of opioid receptors naloxone examined in parallel were inactive. The stimulating effect of beta-endorphin and immunorphin on T lymphocyte proliferation is not inhibited by naloxone. Studies on receptor binding of (125)I-labeled immunorphin to T lymphocytes revealed that it binds with high affinity to naloxone-insensitive receptors (K(d) = 7.0 +/- 0.3 nM). Unlabeled immunorphin completely inhibits (125)I-labeled beta-endorphin specific binding to naloxone-insensitive receptors on T lymphocytes (K(i) = 0.6 +/- 0.1 nM). Thus, beta-endorphin and immunorphin interact with common naloxone-insensitive receptors on T lymphocytes.
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PMID:Effect of synthetic beta-endorphin-like peptide immunorphin on human T lymphocytes. 1197 Jul 35

The present study reports, for the first time, that the recombinant hsp65 from Mycobacterium leprae (chaperonin 2) displays a proteolytic activity toward oligopeptides. The M. leprae hsp65 proteolytic activity revealed a trypsin-like specificity toward quenched fluorescence peptides derived from dynorphins. When other peptide substrates were used (beta-endorphin, neurotensin, and angiotensin I), the predominant peptide bond cleavages also involved basic amino acids in P(1), although, to a minor extent, the hydrolysis involving hydrophobic and neutral amino acids (G and F) was also observed. The amino acid sequence alignment of the M. leprae hsp65 with Escherichia coli HslVU protease suggested two putative threonine catalytic groups, one in the N-domain (T(136), K(168), and Y(264)) and the other in the C-domain (T(375), K(409), and S(502)). Mutagenesis studies showed that the replacement of K(409) by A caused a complete loss of the proteolytic activity, whereas the mutation of K(168) to A resulted in a 25% loss. These results strongly suggest that the amino acid residues T(375), K(409), and S(502) at the C-domain form the catalytic group that carries out the main proteolytic activity of the M. leprae hsp65. The possible pathophysiological implications of the proteolytic activity of the M. leprae hsp65 are now under investigation in our laboratory.
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PMID:The Mycobacterium leprae hsp65 displays proteolytic activity. Mutagenesis studies indicate that the M. leprae hsp65 proteolytic activity is catalytically related to the HslVU protease. 1204 73

In mammals, prodynorphin codes for three C-terminally extended forms of leu-enkephalin. This is not the case for the anuran amphibian, Bufo marinus. A combination of 3'RACE, RT-PCR and 5'RACE protocols was used to clone and characterize a prodynorphin cDNA from the brain of this amphibian that contained two met-enkephalin sequences. One met-enkephalin sequence was located at the N-terminal of Met(5)-dynorphin A(1-17), and the other met-enkephalin sequence was located in the N-terminal region of B. marinus prodynorphin in a position that aligned with a pentapeptide met-enkephalin site in mammalian proenkephalin. The latter B. marinus met-enkephalin sequence is flanked by sets of paired basic proteolytic cleavage sites. In addition to the extra met-enkephalin sequence and the Met(5)-dynorphin A(1-17) sequence, the B. marinus prodynorphin contained two C-terminally extended forms of leu-enkephalin [alpha-neo-endorphin and dynorphin B(1-13)]. In the toad precursor the alpha-neo-endorphin sequence is identical to human alpha-neo-endorphin. The B. marinus dynorphin B(1-13) sequence differs from human dynorphin B(1-13) by one amino acid (Thr(12) vs. Val(12)). Steady-state analysis suggests that dynorphin B(1-13) and possibly alpha-neo-endorphin may be cleaved to yield leu-enkephalin as an end-product in the amphibian brain. Finally, the alignment of the extra met-enkephalin sequence in the N-terminal of B. marinus prodynorphin with the corresponding met-enkephalin site in mammalian proenkephalin adds support to the hypothesis that the prodynorphin gene arose as a duplication of the proenkephalin gene.
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PMID:Identification of a fourth opioid core sequence in a prodynorphin cDNA cloned from the brain of the amphibian, Bufo marinus: deciphering the evolution of prodynorphin and proenkephalin. 1209 17


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