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)

Biosynthesis and processing of ACTH/beta-lipotropin was studied in Nelson's syndrome pituitary tumor tissue grown in monolayer culture. Radiolabeled peptides were immunoprecipitated and fractionated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS/PAGE). Important findings include: 1) a virtual absence of 13K ACTH or 3.5K beta-endorphin production; 2) evidence indicating the presence of a 24-26K ACTH and beta-LPH containing intermediate (which implies a different order of processing from that reported in the mouse); 3) An extremely rapid rate of turnover and release of ACTH and beta-lipotropin (beta-LPH) similar to that of the mouse AtT20/D16v pituitary tumors. The latter finding is consistent with an intrinsic pituitary cell defect in the pathogenesis of this disorder.
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PMID:Corticotropin/beta-lipotropin biosynthesis, processing, and release in Nelson's syndrome. 627 Jan 78

There is increasing evidence indicating that the production of cytokines and prostaglandins (PG) may be interrelated and is regulated by glucocorticoids (GC). In the present study we examined the effect of the bacterial endotoxin lipopolysaccharide (LPS) and interleukin-1 (IL-1) on the ex vivo production of PGE2 by the dorsal hippocampus of the mouse which contains high levels of receptors to IL-1. The roles of IL-1 receptors and GC in the regulation of LPS- or IL-1-induced PGE2 production were also studied. In control mice the basal rate of PGE2 ex vivo synthesis by slices of dorsal hippocampus was about 250 pg/mg protein/60 min. Intraperitoneal injection of either LPS (1-50 micrograms/mouse) or IL-1 alpha (50-200 ng/mouse) increased the production of PGE2 in a dose-and time-dependent manner. Both LPS and IL-1 alpha induced a maximal 2.5-fold increase in PGE2 production at 6 h after the injections. IL-1 beta was less effective by approximately 30% as compared to IL-1 alpha. In mice treated with the IL-1 receptor antagonist or with the IL-1 antagonist alpha-melanocyte-stimulating hormone (alpha-MSH), the effects of LPS and IL-1 on PGE2 production were completely abolished. Intraperitoneal injections of dexamethasone (DEX) 5 or 30 micrograms/mouse 2 h prior to the administration of IL-1 alpha significantly enhanced the effect of the cytokine on PGE2 production. In mice treated with 100 micrograms DEX/mouse, the facilitatory effect of the lower DEX does in IL-1-induced PGE2 production was abolished.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of bacterial endotoxin and interleukin-1 on prostaglandin biosynthesis by the hippocampus of mouse brain: role of interleukin-1 receptors and glucocorticoids. 756 37

The effect of central administration of interleukin-1 beta on naloxone-precipitated withdrawal in morphine-dependent mice was studied. The degree of physical dependence on morphine was estimated by counting the number of jumps precipitated by naloxone, one of the typical withdrawal signs. Intracisternal (i.c.) administration of interleukin-1 beta (0.01-1 ng/5 microliters per mouse) to morphine-dependent mice 30 min prior to the injection of naloxone (10 mg/kg i.p.) decreased the number of jumps in a dose-dependent manner. The effect of interleukin-1 beta (1 ng) was significantly antagonized when it was co-administered with interleukin-1 receptor antagonist (1 microgram/mouse). These results suggest that centrally administered interleukin-1 beta could attenuate naloxone-precipitated withdrawal in morphine-dependent mice via interleukin-1 receptors in the brain. Co-administration of alpha-melanocyte-stimulating hormone (300 ng/mouse) or alpha-helical corticotropin-releasing factor (CRF)-(9-41), a CRF receptor antagonist (300 ng/mouse), with interleukin-1 beta also antagonized the inhibitory effect of interleukin-1 beta (1 ng). Moreover, i.c. administration of CRF (200 ng/mouse) significantly decreased the number of jumps.
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PMID:Intracisternal administration of interleukin-1 beta attenuates naloxone-precipitated withdrawal in morphine-dependent mice. 767 98

Intracerebroventricular (i.c.v.) administration to mice of the venom tetradecapeptide mastoparan (MP), which binds certain G transducer proteins, resulted in a long-lasting reduction of the supraspinal antinociception induced by opioids and clonidine, the alpha-2 adrenoceptor agonist. The alpha N-acetyl derivative of beta-endorphin-(1-31) (NAC-beta-END; 1 pmol, i.c.v. per mouse) injected 1 hr before an equimolar dose of MP lessened the antagonist activity of the venom peptide on the antinociception induced by D-pen2,5-enkephalin, [D-Ala2]deltorphin II, D-Ala2-N-MePhe4-Gly-ol5-enkephalin and clonidine when evaluated 24 hr later with the tail-flick test. The impairment exerted by MP on these analgesic substances was not altered when NAC-beta-END was administered after the venom peptide. Therefore, the antinociceptive effect depends on which peptide was injected first. The protective activity of NAC-beta-END against MP antagonism of opioid/clonidine antinociception was dose related and exerted at attomolar and femtomolar doses. This finding strengthens the idea of a neural substrate (possibly G proteins) distinct from the opioid receptor enacted by NAC-beta-END to modulate opioid/clonidine antinociception. This research shows that a series of substances, neuropeptides and venoms dissimilarly influence the functional state of G proteins, thus altering the agonist-activated transduction cascade.
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PMID:alpha N-acetyl-beta-endorphin-(1-31) disrupts the diminishing effect of mastoparan on opioid- and clonidine-evoked supraspinal antinociception in mice. 775 81

We measured iodine-125-labeled recombinant human interleukin-1 alpha (125I-IL-1 alpha) binding in the hippocampus, pituitary, liver, spleen and testis, and plasma adrenocorticotropic hormone (ACTH) and corticosterone levels after i.p. injection of various dose and treatment regimens of the bacterial endotoxin, lipopolysaccharide (LPS). Plasma ACTH and corticosterone levels were significantly increased at 2 h after acute administration of LPS (60 or 300 micrograms/mouse). 125I-IL-1 alpha binding in all peripheral tissues examined was significantly and comparably decreased at 2 h after a single injection of 30 micrograms or 300 micrograms LPS/mouse. On the other hand, 125I-IL-1 alpha binding in hippocampus was significantly decreased only after high dose administration of LPS (300 micrograms/mouse). In order to evaluate if activation of IL-1 in brain resulting in the observed decrease in 125I-IL-1 alpha binding may require more sustained exposure to endotoxin, we compared the effects of a single injection (60 micrograms/mouse) and two injections of LPS (30 micrograms/mouse each at 0 and 12 h). A single injection of LPS (60 micrograms/mouse) decreased 125I-IL-1 alpha binding in the testis but not in the hippocampus, while two LPS injections (30 micrograms/mouse each at 0 and 12 h) caused dramatic reductions in 125I-IL-1 alpha binding in both the hippocampus and testis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of interleukin-1 receptors and hypothalamic-pituitary-adrenal axis by lipopolysaccharide treatment in the mouse. 795 41

Availability of recombinant growth hormone (GH) and development of long-acting formulations of this material will undoubtedly lead to widespread use of GH in animal industry and in medicine. GH can act, directly or indirectly, on multiple targets, but its influence on the reproductive system and on the hormonal control of reproduction is poorly understood. Overexpression of GH genes in transgenic animals provides a unique opportunity to study the effects of long-term GH excess. Transgenic mice overexpressing bovine, ovine, or rat GH (hormones with actions closely resembling, if not identical to, those of endogenous [mouse] GH), exhibit enhancement of growth, increased adult body size, and reduced life-span as well as a number of endocrine and reproductive abnormalities. Ectopic overexpression of bovine GH (bGH) driven by metallothionein or phosphoenolpyruvate carboxykinase promoters is associated with altered activity of hypothalamic neurons which produce somatostatin, loss of adenohypophyseal GH releasing hormone (GHRH) receptors, and suppression of endogenous (mouse) GH release. Elevation of plasma levels of GH (primarily bGH) and insulin-like growth factor (IGF-I) in these transgenic mice leads to increases in the number of hepatic GH and prolactin (PRL) receptors, in the serum levels of GH-binding protein (GHBP), in the percent of GHBP complexed with GH, and in the circulating insulin levels. In addition, plasma adrenocorticotropic hormone (ACTH) and corticosterone levels are elevated. Plasma levels of luteinizing hormone (LH), as well as its synthesis and release, are not consistently affected, but follicle-stimulating hormone (FSH) levels are suppressed, apparently due to pre- and post-translational effects. Pituitary lactotrophs exhibit characteristics of chronic enhancement of secretory activity, and plasma PRL levels are elevated. Prolactin responses to mating or to pharmacological blockade of dopamine synthesis are abnormal. Reproductive life span and efficiency are reduced in both sexes, with the severity and frequency of reproductive deficits being related to plasma bGH levels. Most transgenic females expressing high levels of bGH are sterile due to luteal failure. Overexpression of human GH which, in the mouse, interacts with both GH and PRL receptors leads to additional endocrine and reproductive abnormalities including stimulation of LH beta mRNA levels and LH secretion, loss of responsiveness to testosterone feedback, overstimulation of mammary glands, enhanced mammary tumorigenesis, and hypertrophy of accessory reproductive glands in males.
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PMID:Neuroendocrine and reproductive consequences of overexpression of growth hormone in transgenic mice. 807 44

Acute low-dose ultraviolet B (UVB) radiation impairs the induction of contact hypersensitivity (CH) and induces tolerance in UVB-susceptible strains of mice when dinitrofluorobenzene (DNFB) is applied to an irradiated skin surface. We are interested in learning the cellular and molecular bases for the existence of UVB susceptibility in certain strains of mice. CH was induced by subcutaneous injections into naive syngeneic C57BL/6 and BALB/c mice of dinitrophenyl (DNP)-derivatized Thy-1(+)-depleted epidermal cells enriched for Ia+ cells (LC/DNP, 2 x 10(4) cells per mouse). Tolerance was detected by applying 185 microg of DNFB epicutaneously to mice treated 2 wk earlier with a putative tolerating regimen and testing CH expression. We found that LC/DNP obtained from C57BL/6 skin 2 h after UVB irradiation (400 J per m2) failed to induce CH and induced DNP-specific tolerance instead; by contrast, similar cells obtained from same or even higher dose (400 J per m2 and 1200 J per m2) UVB-exposed BALB/c skin induced vigorous CH, and no tolerance was detected. In both C57BL/6 and BALB/c mice, Ia+-depleted EC/DNP neither sensitized naive syngeneic mice nor induced tolerance. LC/DNP prepared from unirradiated trunk skin of either C57BL/6 or BALB/c mice and pre-incubated in vitro for 2 h with cis-UCA, TNF-alpha, or IL-10 failed to induce intense CH; instead, all induced DNP-specific tolerance. Pre-incubation of similar LCs with alpha-MSH in vitro for 2 h also failed to induce CH but did not cause tolerance. Thus, single low-dose UVB irradiation alters the immunogenic and tolerogenic potentials of LCs only in UVB-susceptible mice; by contrast, pre-treatment of LCs with UVB-dependent soluble factors can achieve effects similar to UVB irradiation in both UVB-susceptible and -resistant strains of mice. These findings demonstrate that UVB susceptibility in mice may be determined by the production of UVB-dependent soluble factors within UVB-irradiated skin.
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PMID:Ultraviolet B-exposed and soluble factor-pre-incubated epidermal Langerhans cells fail to induce contact hypersensitivity and promote DNP-specific tolerance. 912 22

Peptide E is a 25-amino acid peptide derived from proenkephalin A that was originally isolated from the bovine adrenal medulla. Bovine peptide E (BPE), which possesses a Met- and a Leu-enkephalin sequence at its N- and C-terminus, respectively, has been described as a highly potent and selective mu-opioid receptor agonist. Paradoxically, the frog counterpart of peptide E (FPE), which exhibits only two amino acid substitutions (Met15-->Gln and Leu25-->Met) compared with BPE, was found to be totally devoid of antinociceptive activity. To decipher this apparent discrepancy, we have decided to compare the structural and pharmacological characteristics of FPE, BPE, and the chimeric peptide [Gln15]BPE (Q15BPE). In methanol, all three peptides exhibited virtually the same conformation, the central region of each peptide (residues 10-20) being involved in a regular helix. Intracerebroventricular administration of FPE, BPE, or Q15BPE, at doses up to 1000 ng per mouse, did not induce any analgesic effects, as evaluated by the hot plate and writhing tests, whereas, in the same tests, beta-endorphin at a dose of 100 ng provoked profound analgesia. Concomitant administration of FPE, BPE, or Q15BPE (100 ng) with the aminopeptidase-N inhibitor bestatin (50 microg) or the endopeptidase 24-11 inhibitor thiorphan (10 microg) did not produce analgesic responses. Antinociceptive effects were only observed when very high doses of FPE, BPE, and Q15BPE (10000 ng per mouse) were administered. These data clearly demonstrate that, contrary to what has been previously reported, peptide E is virtually devoid of opioid activity.
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PMID:The proenkephalin A-processing product peptide E, which encompasses two enkephalin sequences, has a much lower opioid activity than beta-endorphin. 1047 88

Depression-like behavior induced by YM643, a consensus interferon-alpha (IFN-alpha), was evaluated with the tail-suspension test in mice and compared with depression-like behavior induced by sumiferon, a natural IFN-alpha. To investigate the mechanism of IFN-alpha-induced depression-like behavior, the effects of the tricyclic antidepressant imipramine, the cyclooxygenase inhibitor indomethacin, the opioid receptor antagonist naloxone, and the selective corticotropin-releasing hormone receptor antagonist CP-154, 526 on IFN-alpha-induced depression-like behavior were evaluated. Intravenously injected YM643 (2 x 10(8)-2 x 10(9) U/kg) and sumiferon (2 x 10(6)-2 x 10(7) I.U./kg) dose-dependently increased immobility time. Repeated s.c. injection of either YM643 (6 x 10(6)-6 x 10(8) U/kg) or sumiferon (6 x 10(4)-6 x 10(6) I.U./kg) for 7 days also dose-dependently increased immobility time. After i.c.v. injection of either YM643 (2 x 10(6) U/mouse) or sumiferon (6 x 10(4) I.U./mouse), significant prolongation of immobility time also was observed. Pretreatment with imipramine (30 mg/kg s.c.) significantly reduced the YM643- or sumiferon-induced increases in immobility time. CP-154,526 (0.3-3 mg/kg s.c.) dose-dependently reduced YM643- or sumiferon-induced increases in immobility time with ID(50) values of 0.6 mg/kg against YM643 and 1.3 mg/kg against sumiferon. However, neither indomethacin (10 mg/kg s.c.) nor naloxone (3 mg/kg s.c.) had any effect on YM643- or sumiferon-induced increases in immobility time. These results suggest that IFN-alpha centrally induces depression-like behavior in mice that can be alleviated with imipramine. The results also suggest that activation of corticotropin-releasing hormone receptors is involved in IFN-alpha-induced depression-like behavior, but the prostaglandin and opioid systems do not participate in this process.
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PMID:Corticotropin-releasing hormone receptors mediate consensus interferon-alpha YM643-induced depression-like behavior in mice. 1060 46

This review focuses on the expression, content, and release of neuropeptides and on their role in the development of obesity in animal models with single-gene mutations. The balance between neuropeptides that contribute to the control of feeding behavior is profoundly and variously altered in these models, supporting the concept of the existence of several types of obesity. The hypothalamic neuropeptide Y (NPY) and the pro-opiomelanocortin (POMC) systems are the networks most studied in relation to energy intake. Both receive information about the nutritional status and the level of energy storage through insulin and leptin signaling mediated by specific receptors located on POMC and NPY neurons present predominantly in the arcuate nucleus (ARC). When leptin signaling is defective, through a defect in either the receptor (Zucker fa/fa rat, cp/cp rat, and db/db mouse) or in the peptide itself (ob/ob mouse), the NPY system is upregulated as shown by mRNA overexpression and increased peptide release, whereas the content and/or release of some inhibitory peptides (neurotensin, cholecystokinin) are diminished. For the POMC system, there is a complex interaction between the tonic inhibition of food intake exerted by alpha-melanocyte-stimulating hormone (alpha-MSH) and the Agouti-related protein at the level of the type 4 melanocortin receptor. The latter peptide is coexpressed with NPY in the ARC. Corticotropin-releasing factor (CRF) is the link between food intake and environmental factors. It not only inhibits food intake and prevents weight gain, likely through hypothalamic effects, but also activates the hypothalamo-pituitary axis and therefore contributes to energy storage in adipose tissue. The factors that prod the CRF system toward the hypothalamic or hypothalamo-pituitary axis system remain to be more clearly defined (comodulators, connections between limbic system and ARC, cellular location, and type of receptors, etc. ). The pathways used by all of these neuromodulators include numerous brain areas, but some interest has returned to the classic ones such as the ventromedial and lateral hypothalamic areas because of the recent discovery of some peptides (orexins and melanin-concentrating hormone for the lateral hypothalamus) and receptors (CRF type 2 in the ventromedial hypothalamus). All of these pathways are redundant and function in a coordinated manner and sometimes by the novel expression of a peptide in an unusual area. The importance of such a phenomenon in obesity remains to be determined. Even if single-gene mutations are exceptions in human obesity, the study of genetic animal models of obesity has greatly contributed to the understanding of the regulation of feeding behavior and will allow researchers to develop new drug treatments for obesity that have to be associated with drastic changes in lifestyle (feeding, work habits, and physical activity) for a complete efficiency.
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PMID:Neuropeptides and obesity. 1105 97


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