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 have shown that corticotropin (ACTH), alpha-endorphin, and enkephalins can regulate antibody responses, which suggested a role for neuropeptides in a regulatory circuit between the immune and neuroendocrine systems. ACTH and structurally related peptides were examined here for regulation of mitogen induction of the lymphokine gamma-interferon (IFN gamma) in C57BL/6 mouse spleen cell cultures. Synthetic ACTH1-39 and a porcine pituitary extract containing ACTH activity were potent suppressors of the IFN gamma response. Synthetic ACTH1-39 suppressed the response by approximately 62% at 1 to 3 microM, whereas the porcine extract suppressed by greater than 90% at 1 to 3 microM ACTH. The greater potency of the pituitary extract was shown to be due to the presence of an additional peptide of Mr 2100 that was reactive with antibodies to the N-terminal region of ACTH (ACTH1-13), possessed potent anti-cellular activity against L cells and various transformed cells, but lacked ACTH biologic activity. The anti-cellular peptide suppressed the IFN gamma response by greater than 99% at 0.05 microM. The ACTH1-39 cleavage products, alpha-melanocyte stimulating hormone (alpha MSH; acetylated and amidated ACTH1-13), and corticotropin-like intermediate lobe peptide (CLIP; ACTH18-39) had no effect on IFN gamma production. ACTH1-24, like ACTH1-39, has full steroidogenesis activity but also had no effect on IFN gamma production, which suggests a dissociation of the immunoregulatory and steroidogenic properties of ACTH1-39. ACTH1-39, and possibly also the anti-cellular 2100 Mr peptide, is initially synthesized as the precursor polyprotein pro-opiomelanocortin (POMC). Enzymatic processing of POMC, first to the active ACTH1-39 or the anti-cellular peptide and then to the inactive smaller peptides, probably plays an important role in regulation of lymphokine and antibody production by ACTH and ACTH-related neuropeptides. This is consistent with the recent demonstration of the production of ACTH-like peptides by lymphocytes.
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PMID:Regulation of lymphokine (gamma-interferon) production by corticotropin. 631 43

The regional distribution of pro-opiocortin-derived peptides and methionine enkephalin was investigated in human brain post-mortem. Sequence-directed radioimmunoassays for beta-endorphin, gamma-lipotropin, adrenocorticotrophin, corticotrophin-like intermediate lobe peptide (ACTH18-39, CLIP) alpha-MSH and methionine enkephalin were used and 40 different human brain areas were assayed. The regional distribution of all the pro-opiomelanocortin-derived immunoreactivities were correlated with highest amounts of beta-endorphin, gamma-lipotropin and ACTH in the hypothalamus, amygdala, periventricular grey, substantia nigra and superior colliculus. The distribution of beta-endorphin, gamma-lipotropin and ACTH did not parallel the distribution of methionine-enkephalin immunoreactivity which was present in the globus pallidus, nucleus accumbens and substantia nigra. Gel exclusion chromatography (G-50) showed that pro-opiocortin-related peptides in the human hypothalamus and periventricular grey separated in positions consistent with the major immunoreactive forms being beta-endorphin, gamma-lipotropin, ACTH and CLIP.
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PMID:Regional distribution of pro-opiomelanocortin-derived peptides in the human brain. 632 29

The biosynthesis of pro-opiomelanocortin (POMC) and related peptides by the intermediate lobe of the pituitary gland was studied in the frog Rana ridibunda using the pulse-chase technique. Analysis of radioactive proteins by dodecyl sulfate polyacrylamide gel electrophoresis showed that during pulse incubations a 36,000 dalton (36K) glycosylated prohormone was synthesized. It disappeared slowly during chase incubations, giving rise to another glycosylated protein (Mr 18K), identified as the N-terminal fragment of POMC. This latter protein was secreted to the incubation medium. High performance liquid chromatography analysis of peptides synthesized during chase incubations revealed the biosynthesis of two peptides related to gamma-MSH, three peptides related to alpha-MSH, one endorphin-related and one CLIP-related peptides. These newly synthesized peptides were slowly secreted to the incubation medium. Among the alpha-MSH related peptides, only the des-N alpha-acetyl alpha-MSH form of the peptide was found to be present within the cells, in contrast to the incubation medium where the presence of des-N alpha-acetyl alpha-MSH and a modified alpha-MSH was demonstrated.
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PMID:Biosynthesis, processing and release of pro-opiomelanocortin related peptides in the intermediate lobe of the pituitary gland of the frog (Rana ridibunda). 650 22

High performance liquid chromatography (HPLC) was used for the separation of many neuropeptides. Chromatography was carried out using a Hitachi Model 638 high performance liquid chromatograph. Peptides and samples from tissue dissolved in an aqueous buffer were injected into a stainless-steel column (4 X 250mm) packed with Hitachi #3053 (octadecylsilane). The aqueous buffer consisted of NaH2PO4 and H3PO4. After a loading phase (0% organic solvent) of 1 min, the peptides were sequentially eluted at room temperature using a gradient of organic solvent (acetonitrile or methanol, 0-60%). The eluted polypeptides were detected by UV absorbance at 220nm, and then they were collected for subsequent bio and radioimmunoassay using a fraction collector. The gradient of methanol or acetonitrile in 0.02M NaH2PO4, 0.1% H2PO4 was useful for separating small molecular peptides. The gradient of acetonitrile in 0.05-0.1M NaH2PO4, 0.1% H2PO4 was useful for separating many neuropeptides including ACTH related peptides. Retention times of chromatographed polypeptides showed good reproducibility. Good reproducibility was also found in peak areas of these peptides. A linear relationship was observed between the doses of peptides and their peak areas. The extracts of rat pituitary neurointermediate lobe showed several peaks of UV absorbance on PHLC; some of them coincided with AVP, oxytocin, alph-MSH, CLIP and beta-endorphin but others were unidentified. AVP immunoreactivity showed one peak which coincided with the AVP peak of UV absorbance, but ACTH immunoreactivity showed 5-6 peaks. Thus, many polypeptides were well separated using HPLC by changing the eluting condition. The simplicity, speed, good reproducibility and good quality of the separations render this technique suitable for purification and quantitative analysis of neuropeptides, and the combination of HPLC, radioimmunoassay and bioassay gives very fine analysis of neuropeptides.
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PMID:[The separation of neuropeptides by high performance liquid chromatography and its application to the analysis of peptides in the rat pituitary neurointermediate lobe (author's transl)]. 680 25

Research from a number of laboratories using of systems has shown that cells from the anterior and intermediate lobes of the pituitary gland, from hypothalamic neurons and from the placenta produce a glycoprotein with the full sequences of corticotropin, beta-lipotropin and gamma-melanotropin. These peptides in turn contain the sequences of alpha- and beta-melanotropin, CLIP, gamma-lipotropin, alpha-, beta- and gamma-endorphins and methionine-enkephalin. The precursor molecule, here called protropin, is processed by the four types of cell to give rise to different ratios of corticotropin, CLIP, beta- and gamma-lipotropin, alpha-, beta- and gamma-endorphins and alpha-, beta- and gamma-melanotropins. The physiological roles of these peptides in neurotransmission, pre- and postnatal endocrinology, mental disorders and neoplasia are only now being established.
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PMID:The intermediate lobe of the pituitary gland: introduction and background. 691 97

In the present review the data supporting the existence at the central level of a stress-sleep relation are reported and discussed. An immobilization stress of 1 or 2 hour(s) is accompanied by a marked polygraphic waking and followed by a significant sleep rebound concerning mainly paradoxical sleep (PS). During the restraint, an important release of 5-hydroxyindoles [5-OHles, a good index of serotonin (5-HT) release] occurs in the basal hypothalamus (BH). This release, produced by the nerve endings originating from the nucleus raphe dorsalis (nRD), might secondarily influence the release and/or the synthesis of hypnogenic substances directly involved in the sleep rebound production. Corticotropin-like intermediate lobe peptide (CLIP, or ACTH18-39) is a peptide possessing hypnogenic properties and derived from proopiomelanocortin (POMC) whose perikarya are contained within the BH (arcuate nucleus). The POMC nerve endings impinge on the nucleus raphe dorsalis, a structure containing sleep permissive components upon which CLIP acts to trigger sleep. It remains to be defined how the activity of the neuronal loop described above is impaired under chronic stress conditions.
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PMID:Evidence for a sleep-promoting influence of stress. 749 9

Two peptides known for their hypnogenic properties, CLIP (corticotropin-like intermediate lobe peptide or ACTH 18-39) or VIP (vasoactive intestinal polypeptide), were injected locally into the nucleus raphe dorsalis (nRD) of rats pretreated with p-chlorophenylalanine (PCPA). During the dark period, the PCPA insomnia was primarily associated with a reduction in paradoxical sleep (PS), whereas both slow wave sleep (SWS) and PS were decreased during the light period. Immunohistochemistry of serotonin in PCPA-pretreated animals indicated a clear disappearance of 5-HT fibers in the basal hypothalamus and the nRD as compared to control animals. Local injections of CLIP or VIP in the nRD restored PS and SWS. The positive injection sites corresponded to the anatomical distribution of either CLIP or VIP fibers, i.e., the entire nRD for VIP and the antero-dorsal part of this nucleus for CLIP. The sleep effects obtained in PCPA-pretreated rats involve a non-5-HT sleep permissive component within the nRD upon which these injected peptides act.
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PMID:Sleep permissive components within the dorsal raphe nucleus in the rat. 758 81

The effects of the POMC-derived peptide CLIP [corticotropin-like intermediate lobe peptide; ACTH(18-39)] and its shorter fragments ACTH(25-39), ACTH(18-24), and ACTH(20-24) on sleep were investigated in rats housed under normal 12-h light/12-h dark conditions (0600 light on). CLIP (10 ng) or equimolar doses of CLIP fragments, respectively, were injected intracerebroventricularly immediately before the 8-h recording period (0800-1600). It was found that paradoxical sleep (PS) was increased by CLIP (+20%) as well as by the N-terminal CLIP fragment ACTH(18-24) (+18%) and by the pentapeptide ACTH(20-24) (+25%), whereas the C-terminal fragment ACTH(25-39) was ineffective. Slow-wave sleep (SWS) was not influenced. These results clearly demonstrate that CLIP and its N-terminal fragments have selective PS-enhancing effects. CLIP and/or CLIP partial sequences are possible candidates for endogenous PS-inducing peptides involved in the physiological regulation of paradoxical sleep.
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PMID:Effects of CLIP (corticotropin-like intermediate lobe peptide) and CLIP fragments on paradoxical sleep in rats. 800 28

Several peptides exhibiting hypnogenic properties when administered i.p., i.v. or i.c.v. are now known. No data, however, are available concerning their targets in the brain. In the present work we hypothesize that the nucleus raphe dorsalis (nRD) may be one such target since it contains 2 sleep permissive components that must be influenced for sleep to occur. One of these components is serotoninergic in nature and gates the occurrence of ponto-geniculo-occipital (PGO) waves. The other, of unknown nature, influences tonic sleep phenomena. For hypnogenic peptides, a putative mechanism permitting the triggering and maintenance of sleep might consist of influencing both the above components. In the present work, 3 hypnogenic substances, CLIP (corticotropin-Like intermediate lobe peptide), VIP (vasoactive intestinal polypeptide) and DSIP (delta sleep inducing peptide), were injected into the nRD in order to determine whether these compounds still induce sleep by local administration. To verify that such local injections do not spread outside the nRD, radiolabelled CLIP and VIP were also injected. Autoradiograms obtained with either labeled CLIP or VIP indicate that these compounds, injected in a 0.2 microliter volume, do not spread outside the nRD. The sleep data obtained confirm that CLIP, at a dose of 10 ng, induces an increase in duration of paradoxical sleep (PS); this effect is observed only for injection sites located in the dorsolateral part of the nRD, an area where CLIP immunoreactive (IR) fibers are present. VIP, at a dose of 100 ng, also increases PS duration, whereas at 10 ng, only slow wave sleep duration is increased. In this case, the positive injection sites are scattered throughout the entire nRD as are the VIP-IR fibers. With DSIP, no sleep effect was found whatever the dose used or the site injected; in the same manner, no DSIP-IR fibers have been located in this structure. These data suggest that the nRD is a target for the expression of the hypnogenic properties of CLIP and VIP, but not for DSIP. The nature of the possible mechanisms permitting such expression are discussed.
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PMID:Is the nucleus raphe dorsalis a target for the peptides possessing hypnogenic properties? 818 Jul 98

Using an indirect immunoperoxidase technique, the location of cell bodies and fibres containing adrenocorticotropin hormone/corticotropin-like intermediate lobe peptide (ACTH/CLIP) was studied in the cat diencephalon. Immunoreactivity was observed in several diencephalic nuclei of the cat in which no immunoreactivity has been previously reported. In this sense, a low density of immunoreactive cell bodies was found in the nucleus ventromedialis hypothalami; a high density of immunoreactive fibres was found in the medial preoptic area; a moderate density in the lateral preoptic area and in the nuclei centralis thalami (pars medialis), interventralis thalami, interanteromedialis thalami, parafascicularis and praemamillaris (pars ventralis and pars dorsalis); a low density in the nuclei habenularis lateralis and reuniens thalami, and single fibres were found in the nuclei lateralis thalami (pars anterior), habenularis medialis, parataenialis, corpus geniculatum mediale, ventralis thalami (pars medialis) and in the fornix. Our results point to a more widespread distribution of ACTH/CLIP immunoreactive structures in the cat diencephalon in comparison with previous studies carried out in the same region of this feline.
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PMID:An immunocytochemical mapping of ACTH/CLIP in the cat diencephalon. 890 60


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