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)

The response profiles of fetal sheep adrenals to tropic stimulation have been examined ih vivo and in vitro. Isolated adrenal cells from sheep fetuses in early pregnancy (Day 50) reduced cortisol in response to ACTH, dibutyryl cyclic AMP and GTP. The response was minimal on Day 100, but reappeared near term. 17 alpha-Hydroxyprogesterone was converted to cortisol by adrenals of all ages, but pregnenolone and progesterone were converted to cortisol only in early and late, but not mid-pregnancy. These studies suggested that the mid-gestation loss of fetal adrenal responsiveness was associated with post-receptor/adenylate cyclase events and involved loss of 17 alpha-hydroxylase activity. Fetal adrenal function was activated by exogenous ACTH in vivo, and was reflected in an increase in the ratio of cortisol to corticosterone in fetal plasma and in augmented cortisol output in vitro from dispersed fetal adrenal cells. The results were consistent with an effect of ACTH administration on 17 alpha-hydroxylation. Fetal pituitary cells, prostaglandin E2, alpha-MSH and term placental extract are other potential (sources of) corticotropins, although further studies are required to delineate the nature and origin of the active substances, and/or their primary sites of action.
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PMID:The development of fetal adrenal function. 627 66

The opioid peptides, beta-endorphin and the enkephalins, exhibit binding to brain tissue that is stereospecific, of high affinity, and saturable; from comparisons of the pharmacological potencies of a number of alkaloids with their abilities to displace peptide binding, it is concluded that peptide binding is probably relevant to pharmacological response for beta-endorphin, but not necessarily for enkephalins. The results of structure-activity studies indicate that both the (1-5) and a C-terminal sequence of the beta-endorphin molecule are necessary for both binding and pharmacological response, while pentapeptide conformation is related to enkephalin binding and pharmacological potency. The binding of opioid peptides possesses a brain regional distribution similar to that of alkaloids, with greatest enrichment in the striate, somewhat lesser amounts in the hypothalamus, thalamus, and amygdala, and least in the cortex and cerebellum; physiochemical properties, including inhibition by Na+, GTP, and by pretreatment of brain tissue with sulfhydryl reagents and proteolytic and lipolytic enzymes, are also similar to those of alkaloids. Other evidence, however, indicates that enkephalins and alkaloids bind to different sites: (1) differences in the abilities of enkephalins and alkaloids to displace labeled enkephalin and labeled alkaloid binding; (2) differences in relative pharmacological potencies of alkaloids and enkephalins in different systems; (3) small but significant differences in brain regional distribution and in certain physicochemical properties; and (4) selective protection of inhibition by irreversible reagents. This evidence, together with other data implicating both proteins and lipids in binding, has led us to propose a model of the beta-endorphin receptor in which the peptide binds to both an enkephalin site, located on a protein, and an alkaloid site, located on a lipid. Binding of enkephalins and beta-endorphin is related to a number of membrane-associated processes that are similarly affected by alkaloid binding, including changes in activity of adenylate cyclase and protein kinase, and in lipid metabolism and calcium ion disposition; some or all of these factors are presumably involved in the mediation of acute and chronic pharmacological effects. All of this work should be greatly aided by isolation of functionally active binding material, and recent work suggests that this breakthrough is finally possible.
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PMID:Opioid peptide receptors and membrane biology. 629 76

In order to explain the differences in the hormone stimulated lipolysis during ontogenic development of rats, the activity of adenylate cyclase was determined in crude plasma membranes of subcutaneous adipocytes of 5, 14, 21 and 45 to 55-day-old animals. Stimulatory effects of nonhormonal and hormonal agents were expressed as the increment in percentage of basal values which were not significantly changed in the age groups studied. The highest stimulatory effect was observed after sodium fluoride in 14 and 21-day-old rats. Guanylylimidodiphosphate and GTP revealed the lowest stimulatory effects in adult animals (greater than 45-day-old). The beta-adrenergic agent isoproterenol revealed the highest stimulatory effect in the 5 and 45-day-old group while in the preparation from 14-day-old rats the adenylate cyclase activity was significantly lower. On the other hand, tetracosactide (beta 1-24-corticotropin) revealed the smallest stimulatory effect on the preparation from 5-day-old rats; its stimulatory effect steadily increased and reached the highest value in adenylate cyclase preparations from adult animals. It can be concluded that the adenylate cyclase system in subcutaneous adipocytes is already basically mature at early ontogenic stages of development in rats. Nevertheless, the explanation for the small variations of the enzyme activity in different age groups requires further study.
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PMID:Adenylate cyclase activity in crude plasma membranes of subcutaneous adipocytes during ontogenetic development of rats. 646 69

The conditions in which Leu(5)-enkephalin inhibition of striatal adenylate cyclase was observed were defined. It was determined that enkephalin inhibition was dependent on GTP. The apparent K(m) for GTP in opiate inhibition was determined to be 0.5 and 2 micrometer when 0.1 mM- and 0.5 mM-ATP were used as substrate. ITP, but not CTP or UTP, could substitute for GTP in the reaction. Though the addition of monovalent cations-Na+, K+, Li+, Cs+, and choline+--stimulated striatal adenylate cyclase activity, enkephalin inhibition of striatal adenylate cyclase did not require Na+ when theophylline was used as the phosphodiesterase inhibitor. Under optimal conditions, i.e., 20 micrometer-GTP and 100 mM-Na+, Leu(5)-enkephalin inhibited the strial adenylate cyclase activity by 23-27%. When the enkephalin regulation of the cyclase activity was further characterized, it was observed that Leu(5)-enkephalin inhibited the rate of the enzymatic reaction. Kinetic analysis revealed that the opioid peptide decreases V (max) values but not the K(m) values for the substrates Mg2+ and Mg-ATP. Agents such as MnCl(2), NaF, and guanyl-5'-ylimido-diphosphate, which directly activated the adenylate cyclase, antagonized the opiate inhibition. Levorphanol and (-)naloxone were more potent than dextrorphan and (+) naloxone in inhibiting adenylate cyclase and in reversing the enkephalin inhibition, respectively. There were differences in the potencies of various opiate peptides in their inhibition of striatal adenylate cyclase activity, with Met5- > Leu(5)-enkephalin > beta-endorphin. The opiate receptor through which the enkephalin inhibition was observed is most likely delta in nature, since in the presence of either Na+ or K+, the magnitude of the alkaloid inhibition was reduced, whereas the peptide inhibition was either potentiated or not affected.
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PMID:Demonstration and characterization of opiate inhibition of the striatal adenylate cyclase. 724 Nov 39

We have previously reported that a beta-endorphin-like substance inhibits phagocytosis in Tetrahymena perhaps by a mu-like opioid receptor. We now report a further characterization of the elements involved in the signal transduction mechanism of this opioid. Affinity chromatography followed by immunoblots of both intracellular extracts and extracellular medium reveal the presence of two main proteins of 64 and 75 kDa. These molecular weights are much higher than that of any known opioid peptide or precursor protein and suggest that we may be dealing with either a novel opioid or with proteins that by chance cross-react with anti-beta-endorphin antibody. Nevertheless, when the biological activity of these proteins was tested it was found that they had an effect similar to that of mammalian beta-endorphin, namely inhibition of phagocytosis by a naloxone-reversible mechanism. We have probed a size-selected Tetrahymena library with a pro-opiomelanocortin probe and have obtained several positive clones; the sequencing of their inserts should establish whether we are dealing with a bona fide member of the opioid family. Another aspect we have been studying is the G-proteins which appear to be involved in the modulation of phagocytosis. We have found, by means of Western blotting (using an antibody against the conserved GTP-binding region of the alpha-subunit), two bands of 51 and 59 kDa; no alpha-subunit of 59 kDa had been reported previously and may represent a novel G-protein. In spite of these differences, the opioid signal transduction mechanism appears to remarkably resemble that present in more complex organisms.
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PMID:A novel opioid mechanism seems to modulate phagocytosis in Tetrahymena. 749 78

A desensitizing protocol to i.c.v. substance P (SP) (from 0.1-10 nmol x 2 at 25-min interval) diminished the supraspinal mu-mediated antinociceptive activity of morphine, D-Ala2-N-MePhe4-Gly-ol5-enkephalin (DAMGO), beta-endorphin-(1-31), D-Ala2-D-Leu5-enkephalin and of the alpha-2 agonist clonidine, whereas the activity of the highly selective delta ligands [D-Pen2,5]-enkephalin and [D-Ala2]-Deltorphin II remained unchanged. This effect was noncompetitive as the slopes for the antinociceptive dose-response curves diminished after SP pretreatment. The antagonism was evident within a few hours after SP and lasted longer than 15 days. The N-acetyl derivative of beta-endorphin-(1-31) (1 pmol) increased the antinociceptive response of DAMGO, D-Ala2-D-Leu5-enkephalin and clonidine, but not of morphine, in SP-pretreated mice. ED80 values of opioid agonists or naltrexone did not prevent SP from reducing the antinociceptive activity of opioids and clonidine. The effect of N-acetyl beta-endorphin-(1-31) was transitory and disappeared within 48 hr, after this period the long-lasting antagonism of SP was revealed. Clonidine (150 nmol) also enhanced opioid antinociception in SP-treated mice. This effect was reversed by the alpha-2 antagonist yohimbine (50 nmol) when given 10 min before clonidine. In mice undergoing treatment with pertussis toxin (0.5 micrograms i.c.v.), an agent that impairs the function of GTP-binding regulatory proteins (Gi/Go), the SP desensitizing protocol did not reduce further the antinociception of DAMGO or morphine. These results suggest a modulatory role for the SP system and the neuropeptide N-acetyl beta-endorphin-(1-31) upon mu and alpha-2 but not delta-mediated supraspinal antinociception in mice.
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PMID:N-acetyl beta-endorphin-(1-31) and substance P regulate the supraspinal antinociception mediated by mu opioid and alpha-2 adrenoceptors but not by delta opioid receptors in the mouse. 768 46

The presence of corticotropin-releasing hormone (CRH) receptors in rat retinal membranes was investigated by using [125I-Tyro]-ovine CRH ([125I]oCRH) as radioligand. The receptor binding was rapid, reversible, saturable and specific. The [125I]oCRH binding was completely displaced by different CRH-related peptides with a rank order of potency similar to that displayed in stimulating rat retinal adenylyl cyclase activity. Two populations of binding sites were detected: one with high affinity (Kd = 1.7 nM) and the other with low-affinity (Kd = 130 nM). The GTP analogue guanosine 5'-O-(3'-thiotriphosphate) reduced the high-affinity binding and increased the relative proportion of sites with low-affinity. Incubation of rat retinal membranes with the RM/1 antibody, which recognizes the carboxyl-terminus of the alpha subunit of the G protein Gs, prevented the CRH stimulation of adenylyl cyclase. In immunoblots, the RM/1 antibody recognized an immunoreactive protein band of 45 kDa and a protein with a similar electrophoretic mobility was ADP-ribosylated by cholera toxin. These data provide evidence for the presence of specific CRH receptors in rat retina and contribute to define the CRH signalling system in this tissue.
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PMID:G protein-coupled corticotropin-releasing hormone receptors in rat retina. 777 Jun 34

Since beta-endorphin is the putative endogenous ligand for epsilon-opioid receptors, the previous demonstration of saturable, high affinity beta-endorphin binding sites on bovine pineal membranes suggests the possible presence of epsilon-opioid receptors. To determine the identity of pineal beta-endorphin binding sites, the inhibition of [125I]beta-endorphin binding by ligands with varying affinities for epsilon-, mu-, delta- or kappa-opioid receptors was investigated. A high positive correlation was observed between the Ki values for these drugs to inhibit [125I]beta-endorphin binding to pineal membranes and for these drugs to bind to delta-opioid receptors but not to mu-, kappa- or epsilon-opioid receptors, demonstrating that in the pineal beta-endorphin binds to delta-opioid receptors. Both NaCl and a GTP analogue were potent inhibitors of [125I]beta-endorphin binding, providing evidence that beta-endorphin is an agonist at pineal delta-opioid receptors. These results suggest that endogenous bovine beta-endorphin may modulate pineal function.
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PMID:Evidence that beta-endorphin is an agonist at bovine pineal delta-opioid receptors. 777 73

In human Y-79 retinoblastoma cells, corticotropin-releasing hormone (CRH) stimulates adenylyl cyclase activity and increases cyclic AMP accumulation. Different CRH analogues mimic the CRH stimulation of adenylyl cyclase and show similar sensitivity to the CRH receptor antagonist alpha-helical CRH9-41. Vasoactive intestinal peptide (VIP) also increases the enzyme activity but less potently than CRH, and its effect is counteracted by the VIP receptor antagonist [D-p-Cl-Phe6,Leu17]VIP. The VIP antagonist does not affect the response to CRH. The CRH-stimulated adenylyl cyclase activity is amplified by Mg2+, is inhibited by submicromolar concentrations of Ca2+, and requires GTP. Moreover, the CRH stimulation is reduced by pretreatment of cells with cholera toxin and by incubation of membranes with the RM/1 antibody, which recognizes the C-terminus of the alpha subunit of Gs. In immunoblots, the RM/1 antibody identifies a doublet of 45 and 52 kDa. Two proteins of similar molecular weights are ADP-ribosylated by cholera toxin. These data demonstrate that in human Y-79 retinoblastoma cells, specific CRH receptors stimulate cyclic AMP formation by interacting with Gs and by affecting a Ca(2+)-inhibitable form of adenylyl cyclase.
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PMID:Coupling of corticotropin-releasing hormone receptors to adenylyl cyclase in human Y-79 retinoblastoma cells. 779 37

In this study we have identified specific binding sites for corticotropin-releasing hormone (CRH) in human Y-79 retinoblastoma cell membranes by using 125I-Tyr-ovine CRH (125I-oCRH) as radioligand. Binding at 19 degrees C was rapid with steady state being reached within 20 min, reversible and linear with membrane protein concentration. The 125I-oCRH binding was enhanced by Mg2+ and inhibited by the GTP analogue guanosine 5'-O-(3'-thiotriphosphate). Y-79 cell membranes exhibited two populations of binding sites, a high-affinity site with an apparent dissociation constant (KD) of 1 nM and a low-affinity site with an apparent KD of 500 nM. 125I-oCRH binding was completely antagonized by human/rat CRH, [Met(O)21]oCRH, alpha-helical CRH9-41, urotensin I, and sauvagine with a rank order of potency similar to that displayed by CRH receptors of other tissues. These data describe for the first time the presence of specific CRH-binding sites in retinal cells. The Y-79 cell line may therefore constitute a valuable model in which to study CRH action on retinal cells.
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PMID:Human Y-79 retinoblastoma cells exhibit specific corticotropin-releasing hormone binding sites. 779 38


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