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)

Intracerebroventricular administration of prototype non-peptide opioid receptor (mu, kappa, sigma) agonists, morphine, ketocyclazocine and N-allyl normetazocine (SKF 10,047) and an agonist at both kappa and sigma receptors, pentazocine, induced hyperthermia in guinea-pigs. Similar administration of peptide opioids like beta-endorphin (BE), methionine enkephalin (Met-E), leucine enkephalin (Leu-E) and their synthetic analogues D-ala2-methionine-enkephalinamide (D-ala2-Met-E) and D-ala2-leucine-enkephalinamide (D-ala2-Leu-E) also caused hyperthermia. Of the three anion transport systems (iodide, hippurate and liver-like) present in the choroid plexus, only the liver-like transport system seems to be important to central inactivation of beta-endorphin, D-ala2-Met-enkephalin and D-ala2-Leu-enkephalin since iodipamide (an inhibitor of the liver-like transport system) augmented the hyperthermia. Prostaglandins (PG) and norepinephrine (NE) were not involved in peptide- and non-peptide opioid-induced hyperthermia because a prostaglandin synthesis inhibitor, indomethacin, and an alpha-adrenergic receptor blocker, phenoxybenzamine, had no thermolytic effect. Likewise cAMP was not required since a phosphodiesterase inhibitor, theophylline, did not accentuate the hyperthermia due to administration of peptide and non-peptide opioids. Naloxone-sensitive receptors were involved in the induction of hyperthermia by morphine and beta-endorphin since naloxone attenuated the effect. In contrast, the hyperthermic responses to ketocyclazocine, SKF 10,047, pentazocine, Met-enkephalin, Leu-enkephalin, D-ala2-Met-enkephalin and D-ala2-Leu-enkephalin were not antagonized by naloxone. Lack of antagonism of naloxone on pyrogen, arachidonic acid, PGE2, dibutyryl cAMP and NE-induced hyperthermia indicates that endogenous opioid peptides are not likely to be central mediators of the hyperthermia induced by these agents.
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PMID:Hyperthermic responses to central injections of some peptide and non-peptide opioids in the guinea-pig. 687 39

Ether-laparotomy stress resulted in a dramatic decrease in specific iodine-125-labeled ovine CRF binding ([125I]oCRF) in the pituitary at 6 h after the onset of the stress although it did not affect [125I]oCRF binding in the pituitary at 2 h after the stress. [125I]oCRF binding was unchanged in the frontal cortex after the stress. In contrast, [125I]interleukin-1 (IL-1)alpha binding was significantly increased in the pituitary at 2 h after the stress and tended to be higher than non-stressed levels at 6 h after the stress but was not statistically significant. Ether-laparotomy stress did not affect [125I]IL-1 alpha binding in hippocampus, spleen and testis at any time after the stress. Plasma adrenocorticotropic hormone (ACTH) and corticosterone were increased at 2 h after the stress. These data demonstrate complex interactions between CRF and IL-1 receptors on HPA axis during stress.
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PMID:Reciprocal modulation of corticotropin-releasing factor and interleukin-1 receptors following ether-laparotomy stress in the mouse. 782 96

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

Increased levels of 5-hydroxyindole acetic acid (5-HIAA) were found in a patient with a tumor arising in the middle ear. Iodine-123-metaiodobenzylguanidine ([123I]MIBG) scintigraphy and biochemical analysis showed evidence of serotonin production by the tumor. Immunohistochemistry of the tumor showed reactivity with antibodies directed against serotonin, chromogranin, leu-7 and neuron-specific enolase; S-100, met-enkephalin, leu-enkephalin and glial fibrillary acid protein were negative. This case suggests a close relationship between functioning paragangliomas and carcinoid tumors because a strong clinical and endocrinological resemblance exists. The hormonal activity found is discussed in relation to extra-adrenal paragangliomas. We recommend urinary screening not only for detection of increased levels of catecholamines, but also of 5-HIAA in all patients with paragangliomas of the head and neck. When elevated levels are found, [123I]MIBG scintigraphy should be performed to localize the areas of increased uptake in or outside the head and neck region.
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PMID:Carcinoid tumor of the jugulo-tympanic region. 866 59

Two peptides of potential utility for targeting melanoma cells, alpha-melanocyte-stimulating hormone (alpha-MSH) and its more potent analogue [Nle4,D-Phe7]-alpha-MSH, were radioiodinated in 45-65% yield using N-succinimidyl 3-[125I]iodobenzoate (SIB). To determine whether this labeling method resulted in improved in vitro and in vivo characteristics, these peptides also were labeled with 131I by direct iodination with the iodogen method. For alpha-MSH, the rapid tissue clearance of both radionuclides in mice was consistent with rapid degradation of the peptide; however, significantly lower levels of 125I were observed in thyroid and stomach, reflecting a greater inertness to deiodination. More extensive comparisons were performed with [Nle4,D-Phe7]-alpha-MSH. The in vitro binding of [Nle4,D-Phe7,Lys11-(125I)IBA]-alpha-MSH (prepared using SIB) to the murine B-16 melanoma cell line, 34.1 +/- 4.7%, was more than twice as high as that for [Tyr2(131I),Nle4,D-Phe7]-alpha-MSH (15.0 +/- 0.1%), and its KD was more than 10-fold lower than that for conventionally labeled peptide (10 +/- 5 versus 140 +/- 14 pM). The normal tissue clearance of [Nle4,D-Phe7,Lys11-(125I)IBA]-alpha-MSH in mice was faster than that of [Tyr2(131I),-Nle4,D-Phe7]-alpha-MSH. The 19-40-fold lower activity concentrations of [Nle4,D-Phe7,Lys11-(125I)IBA]-alpha-MSH in tissues accumulating free iodide (thyroid and stomach) suggest a greater inertness of this peptide to deiodination. The primary urinary catabolite of [Nle4,D-Phe7, Lys11-(125I)IBA]-alpha-MSH was the lysine conjugate of iodobenzoic acid, whereas radioiodide was the chief catabolite generated from [Tyr2(131I),Nle4,D-Phe7]-alpha-MSH. We conclude that further evaluation of [Nle4,D-Phe7,Lys11-(125I)IBA]-alpha-MSH for targeting alpha-MSH receptors is warranted and that SIB may be a useful method for the radioiodination of peptides.
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PMID:Enhanced binding and inertness to dehalogenation of alpha-melanotropic peptides labeled using N-succinimidyl 3-iodobenzoate. 898 45

An analogue of human melanin-concentrating hormone (MCH) suitable for radioiodination was designed in which Tyr13 and Val19 of the natural peptide were replaced by phenylalanyl and tyrosyl residues: [Phe13, Tyr19]-MCH. The peptide was synthesized by the continuous-flow solid-phase methodology using Fmoc-strategy and polyhipe PA 500 and PEG-PS resins. The linear MCH peptides with either acetamidomethyl-protected or free cysteinyl residues were purified to homogeneity and cyclized by iodine oxidation, yielding the final product with the correct molecular weight of 2434.61. Radioiodination of the C-terminal tyrosine was carried out enzymatically using solid-phase bound glucose oxidase/lactoperoxidase, followed by purification on a reversed-phase mini-column and by high-pressure liquid chromatography. The resulting [125I]-[Phe13, Tyr19]-MCH tracer was the first radiolabelled MCH peptide suitable for radioreceptor assay: saturation binding analysis using mouse G4F-7 melanoma cells demonstrated the presence of 1090 MCH receptors per cell. The dissociation constant (KD) was 1.18 x 10(-10) M, indicating high-affinity MCH receptors on these cells. MCH receptors were also found in other cell lines such as mouse B16-F1 and G4F and human RE melanoma cells as well as in PC12 and COS-7 cells. Competition binding analyses with a number of other peptides such as alpha-MSH, neuropeptide Y, substance P and pituitary adenylate cyclase activating peptide, demonstrated that the binding to the MCH receptor is specific. Atrial natriuretic factor was found to be a weak competitor of MCH, indicating topological similarities between MCH and ANF when interacting with MCH receptors.
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PMID:Synthesis and iodination of human (phenylalanine 13, tyrosine 19) melanin-concentrating hormone for radioreceptor assay. 922 84

Adult male mice were treated with di-isopropylfluorophosphate (DFP), a neurotoxic organophosphate which crosses the blood brain barrier, or ecothiophate (phospholine iodide) which has been reported to be non-neurotoxic. The presence of immunoreactivity for the pro-opiomelanocortin (POMC)-derived peptides beta-endorphin and alpha-melanotropin was examined in intramuscular nerves in diaphragm, extensor digitorum longus (EDL) and soleus muscles, and in motoneurones in the cervical and lumbar regions of the spinal cord, up to 5 days after the treatment. The incidence of both immunoreactive intramuscular nerves and immunoreactive ventral horn cells was increased after administration of either DFP or ecothiophate but the extent of the increase and the time course depended on the muscle type or spinal cord region being examined. The effect of the treatment on the expression of POMC mRNA was investigated using in situ hybridization. The proportion of ventral horn cells which expressed the mRNA was significantly increased by 3h after ecothiophate administration. It reached a peak at 24 h but had returned to normal by 48 h. The results indicate that organophosphates can increase the expression of POMC-derived peptides in motoneurones whether the compounds cross the blood-brain barrier freely or not. This effect may be a consequence of their action to inhibit acetylcholinesterase at the neuromuscular junction and may be part of a regenerative response.
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PMID:Effect of organophosphate administration on the expression of pro-opiomelanocortin-derived peptides in motoneurones. 986 68

A photoreactive analogue of human melanin-concentrating hormone was designed, [D-Bpa13,Tyr19-MCH, containing the D-enantiomer of photolabile p-benzoylphenylalanine (Bpa) in position 13 and tyrosine for radioiodination in position 19. The linear peptide was synthesized by the continuous-flow solid-phase methodology using Fmoc-strategy and PEG-PS resins, purified to homogeneity and cyclized by iodine oxidation. Radioiodination of [D-Bpa13,Tyr19]-MCH at its Tyr19 residue was carried out enzymatically using solid-phase bound glucose oxidase/lactoperoxidase, followed by purification on a reversed-phase mini-column and HPLC. Saturation binding analysis of [125I]-[D-Bpa13,Tyr19]-MCH with G4F-7 mouse melanoma cells gave a K(D) of 2.2+/-0.2 x 10(-10) mol/l and a B(max) of 1047+/-50 receptors/cell. Competition binding analysis showed that MCH and rANF(1-28) displace [125I]-[D-Bpa13,Tyr19]-MCH from the MCH binding sites on G4F-7 cells whereas alpha-MSH has no effect. Receptor crosslinking by UV-irradiation of G4F-7 cells in the presence of [125I]-[D-Bpa13,Tyr19]-MCH followed by SDS-polyacrylamide gel electrophoresis and autoradiography yielded a band of 45-50 kDa. Identical crosslinked bands were also detected in B16-F1 and G4F mouse melanoma cells, in RE and D10 human melanoma cells as well as in COS-7 cells. Weak staining was found in rat PC12 phaeochromocytoma and Chinese hamster ovary cells. No crosslinking was detected in human MP fibroblasts. These data demonstrate that [125I]-[D-Bpa13,Tyr19]-MCH is a versatile photocrosslinking analogue of MCH suitable to identify MCH receptors in different cells and tissues; the MCH receptor in these cells appears to have the size of a G protein-coupled receptor, most likely with a varying degree of glycosylation.
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PMID:(D-(p-benzoylphenylalanine)13, tyrosine19)-melanin-concentrating hormone, a potent analogue for MCH receptor crosslinking. 1036 6

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is a new diabetic strain of rats whose disease closely resembles human type 2 diabetes. We measured plasma adrenocorticotropic hormone (ACTH) and corticostrone levels, and iodine-125-labeled ovine corticotropin-releasing factor ([125I]oCRF) binding in the anterior pituitary after ether-laparotomy stress in OLETF rats to examine the alteration of the hypothalamic-pituitary-adrenal (HPA) axis. In addition, we examined ACTH secretion following CRF administration in vivo and in vitro to characterize the mechanisms regulating the HPA axis in OLETF rats. Body weight, plasma glucose and insulin levels in OLETF rats were significantly higher than that in Long-Evans Tokushima Otsuka (LETO) rats. Basal plasma ACTH levels tended to be higher in OLETF rats than in LETO but it did not reach statistical significance. Ether-laparotomy stress dramatically increased plasma ACTH levels at 2 h after the stress both in either OLETF and LETO rats; the peak plasma ACTH level in OLETF rats following the stress was significantly greater than in LETO rats. Plasma ACTH levels following CRF (2 microg/kg, i.v.) in OLETF and LETO rats showed statistically significant increases at 10 and 30 min after CRF administration compared to ACTH levels at 0 min, however, the peak plasma ACTH level in OLETF rats at 10 min after CRF administration was significantly greater than in LETO rats. In contrast to ACTH levels, no significant differences in corticosterone levels between OLETF and LETO were observed at any of the time points. CRF (10 ng/ml) significantly increased ACTH secretion in pituitary cultures from OLETF compared to LETO rats. These data reveal a complex regulation of the endocrine system in this diabetic condition and suggest that HPA axis may be more stimulated during acute stress in diabetes mellitus than in unaffected subjects.
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PMID:Increased adrenocorticotropin responses to acute stress in Otsuka Long-Evans Tokushima Fatty (type 2 diabetic) rats. 1066 2

The Ignalina Nuclear Power Plant consists of two Russian-made RBMK-1500 reactors. The plant uses Lake Druksiai as a natural reservoir for cooling water. Within the framework of the revised radiation dose limitation system, site-specific routine release conversion factors and maximum annual effective doses for the dominant radionuclides and pathways were evaluated for both atmospheric and aquatic releases. Using calculated release conversion factors, the locations of the highest predicted activity concentrations were determined for air and for the dilution zone of heated effluent water during the period 1984-1998. Committed effective doses for critical group members were less than 0.001 mSv for Ignalina Nuclear Power Plant airborne releases and less than 0.05 mSv for aquatic releases. These dose estimates are lower than the 1 mSv dose limit for the adjacent population. In the case of Ignalina Nuclear Power Plant, taking into account the uncertainties, a recommendation for the administrative dose constraint is 0.25 mSv y(-1). This dose level may scarcely affect human health. Interestingly, during screening for thyroid disorders, endocrinologists and pediatric-endocrinologists determined a dominance of abnormal thyroids (up to 60%) among school children in the vicinity of Ignalina NPP. The data on neonatal screening for congenital hypothyroidism and transient hyperthyrotropinemia, however, suggested a possibility that the majority of abnormal thyroid cases were related to stable iodine deficiency. Thus, the influence of Ignalina Nuclear Power Plant on thyroid disorders is highly conjectural and unlikely to be associated with the observed levels of childhood thyroid disease.
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PMID:Environmental releases of radioactivity and the incidence of thyroid disease at the Ignalina Nuclear Power Plant. 1108 3


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