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)

Melanin was measured in various parts of the rat brain by a spectrophotofluorometric assay. This method could detect natural, Sepia melanin as well as melanin synthesized from L-DOPA. Contrary to published expectations of other investigators, measurable amounts of melanin were found in the brain of albino as well as pigmented rats. The highest concentrations of melanin occurred in the pons-medulla and midbrain, but all regions within the blood-brain barrier contained greater concentrations than samples from many other tissues in the body. No significant change in the melanin content was found after various endocrine manipulations such as removal of the pituitary, pineal, adrenals, thyroid, testes, or ovaries, exposure to constant illumination or darkness, and daily injection for 5 weeks of alpha-MSH, Pro-Leu-Gly-NH2 (MIF-I) or melatonin. As expected, retinal tissue from black-hooded rats contained extremely high levels of melanin whereas that from albino rats contained no melanin. It is thought that the presence of melanin in the brain of albino and pigmented rats may have a function which is still unknown.
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PMID:Melanin in the rat brain. 102 Dec 12

Two natural occurring melanotropins, camel betaC2-MSH and bovine beta-MSH, have been synthesized by improved solid-phase procedures. The coupling reaction of tert-butyloxycarbonylamino acids was achieved by using their preformed symmetrical anhydrides. The synthetic hormones were purified by gel filtration on Sephadex G-10 and G-25, chromatography on carboxymehtylcellulose, and partition chromatography on Sephadex G-25 with final yields of 56 and 35% for betac2-MSH and betab-MSH, respectively. They were then shown to be identical with their natural hormones in amino acid analysis, paper electrophoresis, disc electrophoresis, thin-layer chromatography, enzymic digests, and bioassays. Bioassay data of these two synthetic melanotropins indicate that the replacement of Ser by Gly in betab-MSH does not change its melanocyte-stimulating activity.
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PMID:Synthesis and biological activity of camel and bovine beta-melanotropins. 125 60

The objective of this study was to determine if there are age-related alterations in hemodynamic and/or neuroendocrine responses to the mu-opioid receptor agonist, [D-Ala2,MePhe4,Gly(ol)5] enkephalin (DAMGO), or corticotropin releasing hormone (CRH) administered centrally. To this end, DAMGO (1-3 nmoles) or CRH (1 nmole) was injected intracerebroventricularly (icv) to freely moving young (6-8 month) and aged (24-26 month) Fischer 344 male rats. Blood pressure, heart rate (HR), and plasma concentrations of norepinephrine (NE), epinephrine (EPI), adrenocorticotropin (ACTH), and prolactin (PRL) were measured over time. Under basal conditions, NE levels were higher and blood pressures were lower in aged rats, whereas there were no significant differences in EPI, ACTH, or PRL levels. The stimulatory effect of DAMGO on blood pressure, HR, and plasma EPI and ACTH was attenuated, but the PRL response was enhanced in aged cohorts. In contrast, there were no age-related differences in the NE responses to DAMGO or CRH nor in CRH-induced increases in EPI or ACTH. The sympathoadrenal and hemodynamic effects of DAMGO were blocked by naloxone in both age groups. These results indicate that alterations in mu-opioid function with age are specific for the opioid system and do not reflect a generalized decline in central regulation of neuroendocrine and cardiovascular function.
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PMID:Selective impairment of neuroendocrine and hemodynamic responses to a mu-opioid peptide in aged rats. 131 52

Mouse brains of various ages from embryonal day 14 (E14) to adult were analyzed for opioid receptor binding using the enkephalin analog Tyr-D-Ala-Gly-NMe-Phe-Gly-ol (DAMGE) and the opiate alkaloid dihydromorphine (DHM) as mu-selective radioligands. Binding parameters were estimated from homologous and heterologous competition binding curves. During the postnatal period, Kd values for [3H]DAMGE did not change but Bmax values (fmol/mg protein) increased 2.7 fold from postnatal day 3 (P3) to P7. Minor receptor density fluctuations were evident from P7 to adult. Similar results were obtained with [3H]DHM. In contrast, estimation of total mu binding sites (fmol/brain) revealed a continuous rise from P3 to the adult. The postnatal developmental profile of total mu binding sites was comparable to the weight gain of mouse brain and the increase in protein content. In contrast, during the same period beta-endorphin immunoreactivity (IR) levels undergo an increase that is inversely proportional to mu opioid receptor Bmax values. [3H]DAMGE binding to E14 membrane preparations was inhibited to a greater extent by Gpp(NH)p than that to P1 or adult. Additional characterization of mu receptors was accomplished by heterologous competition binding assays. IC50 values for beta-endorphin in competition with [3H]DHM and [3H]DAMGE were age dependent and differed for the two radioligands. These results suggest that mu receptor selectivity for mu-specific peptide and alkaloid ligands changes as a function of age.
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PMID:Differential development of beta-endorphin and mu opioid binding sites in mouse brain. 131 73

We have investigated the pharmacological profile of the opioid stimulation of adenylate cyclase activity in rat olfactory bulb, in order to identify the opioid receptor subtype(s) involved in this response. The synthetic delta-selective agonists (D-Ala2)deltorphin I, (2-D-penicillamine,5-D-penicillamine)-enkephalin, and (D-Ser-Leu5-enkephalyl)-threonine were effective stimulators of the enzyme activity, with EC50 values of 6.7, 420, and 63 nM, respectively. A significant increase was also observed with the mu-selective agonists (N-methyl-Phe3,D-Pro4)-morphiceptin, dermorphin, and (D-Ala2-N-methyl-Phe4-Gly-ol5)-enkephalin (DAGO). The latter two agonists displayed biphasic concentration-response curves, with high affinity components accounting for 75-80% of the maximal responses. The kappa-selective agonists U-50,488 and U-69,593 were ineffective, whereas (D-Ala2)dynorphin A-1-11, dynorphin A, dynorphin A-1-13, and dynorphin A-1-6 acted with a rank order of potency consistent with their affinity for delta receptors. The stimulatory responses of Leu-enkephalin, beta-endorphin, dynorphin A, and delta-selective agonists were counteracted by naltrindole with pA2 values of 9.39-8.93, whereas naloxone was less potent (pA2 = 8.17-7.59). The kappa-selective antagonist norbinaltorphimine was the least potent. The inhibition by naltrindole and naloxone of DAGO stimulation showed biphasic curves, with 90% of the response being antagonized more potently by naloxone than by naltrindole. These results demonstrate that delta- and mu- but not kappa-opioid receptor subtypes stimulate basal adenylate cyclase activity in rat olfactory bulb.
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PMID:Characterization of opioid receptors mediating stimulation of adenylate cyclase activity in rat olfactory bulb. 132 51

Peptides that are derived from the processing of proopiomelanocortin were isolated in pure form from the brain of the frog Rana ridibunda. The primary structure of the most abundant of those peptides was established as: Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val. This amino acid sequence is identical to that of mammalian and frog pituitary alpha-melanocyte-stimulating hormone (MSH) and the peptide co-eluted with synthetic desacetyl alpha-MSH, indicating that it is COOH-terminally alpha-amidated. A second component, which exhibited a shorter retention time, co-eluted with the glycine-extended form of desacetyl alpha-MSH [ACTH(1-14)]. The primary structure of the third peptide isolated in pure form from the brain extract was established as: Lys-Tyr-Val-Met-Ser-His-Phe-Arg-Trp-Asn-Lys-Phe-NH2. This sequence corresponds to Lys-gamma 1-MSH as predicted from the nucleotide sequence of frog proopiomelanocortin. The presence of substantial amounts of desacetyl alpha-MSH and Lys-gamma 1-MSH in the frog brain supports the concept that, in amphibia, melanotropins may act as neurotransmitters and/or neuromodulators as well as hormonal peptides.
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PMID:Isolation and structural characterization of peptides related to alpha- and gamma-melanocyte-stimulating hormone (MSH) from the frog brain. 133 55

Possible involvement of adenosine, as a secondary neurotransmitter, in opioid modulation of nociception and gastrointestinal function was investigated in mice. Inhibitory actions of theophylline, a nonselective adenosine receptor antagonist, were evaluated against effects evoked by opioid receptor-selective agonists administered at spinal or supraspinal sites. Intrathecal administration of theophylline significantly inhibited antinociceptive actions produced by intrathecal (i.th.) injections of morphine, [D-Ala2, NMPhe4, Gly-ol] enkephalin (DAMGO), [D-Pen2, D-Pen5] enkephalin (DPDPE) and beta-endorphin as measured with the warm water tail-flick assay. The rank order of rightward displacement of i.th. agonist dose-response curves by theophylline (i.th.) was DPDPE (greatest) > DAMGO > morphine > beta-endorphin. Theophylline was less effective as an inhibitor in the hot-plate assay. Additionally, i.th. administration of theophylline inhibited antinociceptive effects evoked by i.c.v. administration of opioids. The rank order of rightward displacement of dose-response curves after i.c.v. opioid administration was DAMGO (greatest) > beta-endorphin > morphine > DPDPE. In contrast to the effectiveness of theophylline administered i.th., theophylline coadministered i.c.v. with opioid agonists did not inhibit opioid-induced antinociception. Neither i.th. nor i.c.v. theophylline altered inhibitory effects on gastric emptying and gastrointestinal propulsion produced by i.th. or i.c.v. administration of selective opioid agonists. These data provide additional support for involvement of spinal adenosine as a secondary neurotransmitter in opioid antinociceptive processes associated with local spinal reflexes as well as in descending antinociceptive processes. Adenosine was not involved in modulation of opioid-activated gastrointestinal outflow pathways at either spinal or supraspinal levels.
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PMID:Involvement of adenosine in antinociception produced by spinal or supraspinal receptor-selective opioid agonists: dissociation from gastrointestinal effects in mice. 133 55

Melanocyte stimulating hormone (alpha-MSH, alpha-melanotropin),Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Ly-Pro-Va l-NH2, regulates melanogenesis within epidermal melanocytes of many animals. An MSH analogue ([Nle4,D-Phe7]alpha-MSH) that exhibits superpotency and prolonged biological activity has been synthesized, biologically characterized, and is presently in clinical trials to determine its possible clinical use in tanning of the skin. It also has potential for the diagnosis, localization, and chemotherapy of melanoma. The effects of this analogue on the growth, metastatic behavior, and invasive potential of a melanotic variant of Cloudman S-91 murine melanoma are reported here. In an intracutaneous murine model of melanoma cell tumor growth, the analogue did not increase primary tumor growth (size) after the period of administration of the peptide hormone analogue and did not affect spontaneous lung metastases. Survival times for the control and melanotropin-treated groups were similar, suggesting that overall tumor burden was not affected by treatment with the hormone analogue. Last, melanoma cell invasion through a human amniotic basement membrane in vitro was not enhanced compared to untreated cells.
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PMID:Effects of a melanotropic peptide on melanoma cell growth, metastasis, and invasion. 133 2

Whereas endopeptidase 24.11 cleaves the Gly-Phe bond in both Met- and Leu-enkephalin, endopeptidase 24.15 rapidly converts dynorphin A1-8, alpha and beta-neoendorphin into Leu-enkephalin, and Met-enkephalin-Arg6-Gly7-Leu8 (MERGL) into Met-enkephalin. Inhibitors of both endopeptidase 24.11 and endopeptidase 24.15 each produce antinociception, and inhibitors of endopeptidase 24.11 increase the magnitude of enkephalin antinociception. The present study compared the central antinociceptive effect of an inhibitor of endopeptidase 24.15, N-[1-(R-S)-carboxy-3-phenylpropyl]-Ala-Ala-Phe-p-aminobenzoate (cFP-AAF-pAB) with one of endopeptidase 24.11 N-[1-(RS)-carboxy-3-phenylpropyl]-Phe-p-aminobenzoate (cFP-F-pAB) upon central opioid antinociception induced by MERGL, metenkephalin and dynorphin A1-8. cFP-AAF-pAB, but not cFP-F-pAB increased MERGL antinociception on the tail-flick and jump tests. In contrast, cFP-F-pAB, but not cFP-AAF-pAB increased met-enkephalin antinociception. Whereas central dynorphin A1-8 failed to induce antinociception itself, co-administration of cFP-AAF-pAB and dynorphin A1-8 increased nociceptive thresholds. This effect was not accompanied by motor dysfunction, but was blocked by systemic pretreatment with naloxone or central pretreatment with naltrexone or nor-binaltorphamine, but not beta-funaltrexamine. These data indicate that endopeptidase 24.15 may be responsible for the degradation of specific opioid peptides (e.g., MERGL, dynorphin), and that this process may prevent the full expression of their antinociceptive properties.
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PMID:Endopeptidase 24.15 inhibition and opioid antinociception. 134 91

Calcitonin gene-related polypeptide (CGRP) was purified from ovine hypothalamic extracts. Its amino acid sequence was determined as: Ser-(Cys)-Asn-Thr-Ala-Thr-(Cys)-Val-Thr-His-Arg-Leu-Ala-Gly-Leu-Leu-Ser- Arg-Ser - Gly-Gly-Val-Val-Lys-Ser-Asn-Phe-Val-Pro-Thr-Asn-Val-Gly-Ser-Gln-Ala-Phe- NH2. This sequence differs from rat CGRP by two amino acid substitutions (Ser for Asp25 and Gln for Glu35). Adenylate cyclase stimulating activity in rat pituitary cell cultures was monitored during the isolation. CGRP had adenylate cyclase stimulating activity comparable to corticotropin-releasing hormone, suggesting a hypophysiotropic role for CGRP. This is the first chemical characterization of CGRP in the brain (hypothalamus).
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PMID:Identification of calcitonin gene related peptide in ovine hypothalamic extract. 141 24


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