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)

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

The transport of ebiratide, a novel adrenocorticotropic hormone (ACTH) analogue, [H-Met-(O2)-Glu-His-Phe-D-Lys-Phe-NH(CH2)8-NH2], through the blood-brain barrier was directly demonstrated in-vivo. [125I]Ebiratide (16.9 MBq mL-1) or [14C]sucrose (29.2 MBq mL-1) known to be restrictively transported through the blood-brain barrier was infused into the rat internal carotid artery at a flow rate of 50 microL min-1 for 10 min, and after 15 min infusion the distribution volume of each compound in the brain parenchyma was determined by the capillary depletion method. The distribution volume of [125I]ebiratide was 167.8 +/- 62.2 microL (g brain)-1, which was about seven times higher than that of [14C]sucrose (24.9 +/- 4.0 microL g brain)-1, indicating the uptake of ebiratide into brain parenchymal cells. During the infusion into the internal carotid artery, brain microdialysis was simultaneously performed to directly collect the brain interstitial fluid as the dialysate. Radioactivity was detected in the dialysate during the [125I]ebiratide infusion and HPLC analysis of the dialysate revealed that the intact ebiratide accounted for greater than or equal to 80% total radioactivity. The concentrations of [125I]ebiratide and [14C]sucrose in the brain interstitial fluid were estimated based on the relative recovery obtained in the in-vitro recovery study. The brain interstitial fluid/internal carotid arterial blood concentration ratio for [125I]ebiratide was determined to be 1.47 x 10(-2) +/- 0.17 x 10(-2) and was about eight times higher than that for [14C]sucrose (1.92 x 10(-3) +/- 0.36 x 10(-3)), indicating significant transport of ebiratide to the brain interstitial fluid.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In-vivo blood-brain barrier transport of a novel adrenocorticotropic hormone analogue, ebiratide, demonstrated by brain microdialysis and capillary depletion methods. 135 39

Low doses (50-200 pg or 3.1-12.4 fmol) of interleukin 1 (IL-1) infused into the brain of rats produced rapid suppression of various cellular immune responses in peripheral lymphocytes of rats. Fifteen minutes after infusion of purified IL-1 beta into the lateral ventricle, natural killer cell activity, response to phytohemagglutinin stimulation, and interleukin 2 production were markedly suppressed in lymphocytes isolated from blood and spleen. These effects were due to infusion of IL-1 into brain since they did not occur when IL-1 was infused into the cisterna magna (essentially posterior to brain) or was injected intraperitoneally. Effects of IL-1 in brain could be blocked by simultaneous infusion of alpha-melanocyte-stimulating hormone, which is known to block the biological actions of IL-1. To stimulate release of endogenous IL-1 in brain, lipopolysaccharide was infused; this produced similar effects as IL-1, and these effects also were blocked by alpha-melanocyte-stimulating hormone. At longer intervals after infusion of IL-1 and lipopolysaccharide (3, 6, and 24 hr), immune responses returned to baseline or remained suppressed; i.e., "rebound" immunopotentiation did not occur. Finally, IL-1 infusion suppressed cellular immune responses in adrenalectomized animals, thereby showing that the effects of central IL-1 on peripheral cellular immune responses were, at least in part, independent of the stimulatory effect of IL-1 on secretion of adrenal hormones. These results indicate a link from brain to peripheral immune responses by means of action of a cytokine acting in the brain.
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PMID:Intracerebroventricular infusion of interleukin 1 rapidly decreases peripheral cellular immune responses. 254 13

Recent studies have shown that inhibitory feedback mechanisms regulate the release of the endogenous opioid peptides beta-endorphin (acting predominantly at mu opioid receptors in the brain), dynorphin (a kappa opioid receptor ligand) and [Met]enkephalin (a delta opioid receptor ligand) from the rat hypothalamus. By using specific antagonists of the various opioid receptor types, it is shown that the release of these peptides from hypothalamic slices in vitro is not only controlled by homologous (auto)-receptors, but that cross-regulation between the three neuronal opioid receptor types also occurs; thus, the delta receptor antagonist N,N-diallyl-Tyr-Aib-Aib-Phe-Leu increases the release of all three peptides, the mu receptor antagonist D-tetrahydroisoquinoline-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 increases that of beta-endorphin and dynorphin, and the kappa receptor antagonist nor-binaltorphimine increases that of dynorphin; all these effects occur in the presence of tetrodotoxin, indicating a presynaptic site of action. We propose the term "allelo-receptors" to describe this particular form of neuronal regulation in which an endogenous ligand, acting via its own specific receptor, also regulates the release of related peptides which activate different classes of opioid receptors.
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PMID:Presynaptic auto- and allelo-receptor regulation of hypothalamic opioid peptide release. 257 Mar 78

The behaviorally active meiety of ACTH resides in only a few amino acid residues and is independent of its peripheral endocrine effects. Although pituitary hormones may reach the brain through the circulation and by retrograde transport through the portal vessel system, the recent discovery that ACTH as part of a big precursor molecule, pro-opiomelanocortin, is widely distributed throughout the brain suggests that "brain borne" ACTH may be the main supplier of behaviorally active neuropeptides. The biotransformation of pro-opiomelanocortin in the anterior pituitary differs from that in the intermediate/posterior lobe and the brain. Thus, the biotransformation of hormones at the site of release may determine their ultimate function i.e. as a hormone (pituitary) or as a neuropeptide (brain). Structure activity studies, and studies on the biotransformation of ACTH in brain synaptosomes corroborate the hypothesis that ACTH in the brain is a precursor of the second order of neuropeptides involved in adaptive behavior. A great number of studies in a variety of behavioral paradigms has shown that ACTH neuropeptides are involved in (visual) attention and motivation, vigilance and learning and maintenance behavior. Other pro-opiomelanocortin molecules such as beta-endorphin undergo a similar processing. Structure activity studies and biotransformation studies of this hormone have revealed the generation of neuropeptides with neuroleptic-like and psychostimulant properties. The neurohypophyseal hormones vasopressin and oxytocin appear to function as precursor molecules of the second order of potent neuropeptides involved in memory processes. The same may hold for other "brain borne" hormones.
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PMID:Pituitary and hypothalamic hormones as precursor molecules of neuropeptides. 613 43

A Mr 26,000 corticotropin (ACTH)-like material is present in glacial acetic acid extracts of all normal rat extrapituitary tissues. In the present study, beta-melanotropin (beta-MSH) immunoactivity was detected in glacial acetic acid extracts of normal rat extrapituitary tissues. beta-MSH immunoactivity was also present in all extracts (mean +/- SEM, fmol/mg of protein): brain, 71.0 +/- 16.3; stomach, 11.5 +/- 1.6; kidney, 8.9 +/- 0.8; colon, 8.2 +/- 1.1; small intestine, 6.5 +/- 1.1; liver, 4.3 +/- 0.5; and heart, 3.2 +/- 0.5. Except in brain extracts, beta-MSH and ACTH immunoactivities of tissue extracts were strongly correlated to each other (r = 0.79; n = 42). When tissue extracts (except brain) were passed through a Sephadex G-75 (superfine) column, ACTH and beta-MSH immunoactivities were eluted in a single peak corresponding to Mr 26,000. In contrast, for brain extracts, the MrS of major peaks of ACTH and beta-MSH immunoactivities were 4,500 and 8,000, respectively; a smaller peak of Mr 26,000 ACTH/beta-MSH-like material was also eluted. Specific anti-ACTH immunocolumns, which did not bind purified synthetic beta-MSH, adsorbed both ACTH and beta-MSH immunoactivities of all tissue extracts except those of brain. One-third of the beta-MSH immunoactivity in brain extracts adsorbed to the anti-ACTH immunocolumn, but two-thirds of beta-MSH immunoactivity passed through the column. We conclude that ACTH and beta-MSH immunoactivities are present in all normal rat extrapituitary tissues and exist in most tissues on the same molecule. This Mr 26,000 molecule is closely related to the pituitary ACTH/beta-lipotropin common precursor.
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PMID:Corticotropin/lipotropin common precursor-like material in normal rat extrapituitary tissues. 657 17

Previously, we have shown that intracisternal (i.c.) administration of beta-endorphin (an opioid peptide naturally occurring in the brain) to preweanling rats markedly decreases DNA synthesis (an index of cell proliferation) in both brain and liver. This observation is consistent with our hypothesis that endogenous CNS beta-endorphin plays an important role in controlling postnatal growth. The current research specifically undertook to investigate, in 10-day-old rats, whether or not i.c. beta-endorphin-evoked suppression of liver DNA synthesis is actually mediated by spinal opioid receptors and/or by descending endorphinergic pathways. In contrast to the i.c. route of administration, beta-endorphin given directly into the spinal subarachnoid space via intrathecal (i.t.) injection did not alter liver DNA synthesis, yet was able to evoke profound antinociceptive responses. This demonstrates that intracisternally applied beta-endorphin exerts its effect on liver DNA by acting at supraspinal sites, and not by directly stimulating spinal opioid receptors after diffusion from its intracerebral site of injection. As it is possible that beta-endorphin's supraspinal actions may activate a descending inhibitory endorphinergic pathway to reduce DNA synthesis, we conducted studies in rat pups administered naloxone intrathecally. Naloxone i.t. was completely ineffective in preventing beta-endorphin i.c. from inhibiting liver DNA synthesis. On the other hand, i.t. coinjection of naloxone plus beta-endorphin was able to block the analgesic response, while their i.c. coinjection reversed the DNA effect. The results from these studies indicate that opioid systems within the spinal cord do not play a major role in mediating CNS beta-endorphins regulation of DNA synthesis in peripheral tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of the spinal cord in intracisternal beta-endorphin-evoked suppression of liver DNA synthesis in 10-day-old rats. 803 94

The unidirectional brain-to-blood transport system for corticotropin-releasing hormone (CRH) across the blood-brain barrier could be instrumental in the homeostasis of central CRH. To characterize this system, the intracerebroventricular injection of 125I-CRH was used in mice. CRH was rapidly transported out of the brain with a half-time disappearance (t1/2) of 15 min, much faster than albumin (t1/2 = 50 min). Kinetic analysis revealed a saturable component with a low maximum velocity (apaproximately 0.020 nmol x min(-1) x brain(-1)) and low capacity (Michaelis constant approximately 1.4 nmol/brain). Transport was inhibited by verapamil, ouabain, and colchicine but not by cyclosporin. Transport was increased by corticosterone and inhibited by tumor necrosis factor-alpha and beta-endorphin. These results suggest that the specific unidirectional brain-to-blood transport system for CRH is dependent on energy and calcium channels, involves microtubules, is independent of the P-glycoprotein transporter, and is acutely modulated by adrenal steroids, cytokines, and endogenous opiates. This suggests its participation in the control of the stress response.
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PMID:Acute modulation of active carrier-mediated brain-to-blood transport of corticotropin-releasing hormone. 912 40

Abstract Inhibin, a water soluble, non-steroidal glycoprotein hormone that inhibits follicle-stimulating hormone secretion, is produced by the gonads and several non-gonadal tissues (placenta, pituitary and brain). This study describes the presence of inhibin alpha-chain-immunoreactive cells in the adrenal cortex of intact adult male rats and the effects of hypophysectomy and adrenocorticotropin treatment on the expression of inhibin in that gland. In intact rats, the majority of the immunoreactive cells were found scattered in the zona glomerulosa and reticularis. The zona fasciculata contained only a few cells immunopositive for the inhibin alpha-chain. No immunoreactive cells were found in the medulla. Hypophysectomy resulted in a dramatic reduction in alpha-subunit immunoreactivity with only scattered cells observed in the zona glomerulosa and reticularis (0 to 2 cells/section). No immunoreactive cells were found in the zona fasciculata or the medulla. Following supraphysiologic adrenocorticotropin administration to hypophysectomized animals, the number of inhibin alpha-chain-immunoreactive cells significantly increased in each zone of the adrenal cortex. The most prominent changes were seen in the zona reticularis. Interestingly, in the adrenocorticotropin-treated animals scattered immunopositive cells were also present in the medulla. Our results suggest that inhibin-related peptide(s) exist within the adrenal gland and that the expression of these peptides is regulated by adrenocorticotropin. Inhibin-related peptide(s) may, therefore, play a paracrine and/or endocrine role in the adrenal function.
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PMID:Localization of inhibin alpha-subunit immunoreactivity in the rat adrenal cortex. 1921 87

Developing bird embryos may be affected by a number of thyroid disrupting chemicals through maternal transfer. However, thyroid disruption in developing embryos of wild birds remains largely unstudied, especially with respect to exposure to ubiquitous environmental contaminant classes including halogenated flame retardants (HFRs). The objective of the present study was to investigate responses of the hypothalamic-pituitary-thyroid (HPT) axis of developing birds that are exposed to elevated concentrations of HFRs in their environment. Ring-billed gulls (Larus delawarensis) were collected at the external pipping stage (i.e., just prior to hatching) from two sub-populations that are differentially exposed to HFRs in the St. Lawrence River (QC, Canada). Plasma levels of thyroid hormones (THs) and transcription levels of thyroid-related genes in three tissues (i.e., liver, thyroid gland and brain) were related to liver concentrations of HFRs in pipping gulls from these two colonies. Liver polybrominated diphenyl ether (PBDE) concentrations were negatively correlated with plasma total T4 and total T4/T3 in pipping ring-billed gulls. Moreover, plasma TH levels and hepatic PBDE concentrations were correlated with the transcription of genes involved in metabolism (deiodinases type 1, 2 and 3) and synthesis (sodium iodide symporter and thyroglobulin) in the thyroid gland, negative feedback loop (thyrotropin and corticotropin releasing hormones) in the brain and the pituitary and targeted action (TH receptors) in the three tissues of gulls. The present study suggested that the alteration of TH homeostasis in developing wild birds through changes in the transcription of several thyroid-related genes may be related to potential PBDE-mediated effects.
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PMID:Changes in thyroid axis responses in two ring-billed gull sub-populations differentially exposed to halogenated flame retardants. 3010 39


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