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)

Animals exposed continuously for 14 days to ethanol vapor in an inhalation chamber at sufficient ethanol vapor concentration to maintain blood ethanol levels from 100-250 mg/100 ml exhibited approximately 36% lower corticotropin-releasing factor binding and 24% lower adenylate cyclase activity in anterior (AL) and neurointermediate lobe (NIL) membranes of the pituitary gland compared to controls not treated with ethanol. To determine the effect of chronic ethanol exposure on proopiomelanocortin (POMC) biosynthesis, the levels of POMC mRNA in the AL and NIL were quantified by Northern blot and slot blot techniques. Ethanol treatment for 1, 7, or 14 days produced a time-related decrease in POMC mRNA levels, relative to total RNA levels, in both the AL and NIL. Ethanol treatment caused a greater reduction in NIL POMC mRNA than in AL POMC mRNA. Exposure to ethanol vapors for 14 days decreased immunoreactive beta-endorphin in plasma by approximately 82%. The observed reduction of immunoreactive beta-endorphin in plasma after long term exposure of rats to ethanol may be related to the alcohol-mediated decrease in corticotropin-releasing factor binding and adenylate cyclase activity, which, in turn, leads to decreased intracellular POMC levels through reduced production of POMC mRNA in the AL and NIL of the rat pituitary gland.
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PMID:Ethanol exposure decreases pituitary corticotropin-releasing factor binding, adenylate cyclase activity, proopiomelanocortin biosynthesis, and plasma beta-endorphin levels in the rat. 293 42

In a previous study we reported the presence of specific nonopiate beta-endorphin (BE) binding sites in peripheral tissues of the rat (Dave JR, Rubinstein N, Eskay RL: Evidence that beta-endorphin binds to specific receptors in rat peripheral tissue and stimulates the adenylate cyclase-adenosine 3',5'-monophosphate system. Endocrinology 117:1389-1396, 1985). The objective of this study was to determine the effect of chronic ethanol administration in vivo on specific nonopiate binding of BE in hepatic and kidney membranes. Experimental animals were exposed continuously for 14 days to ethanol vapor in an inhalation chamber at vapor levels sufficient to maintain blood ethanol levels greater than 120 mg/100 ml, whereas control animals were maintained in ethanol-free chambers. Chronic ethanol treatment decreased [125I]BE binding to hepatic and kidney membranes by approximately 35%, which was due to a decrease in the number of BE binding sites. Chronic ethanol treatment decreased immunoreactive BE in plasma by greater than 80%. In vitro exposure of hepatic and kidney membranes from control animals to ethanol resulted in a dose-related enhancement of BE binding with maximal enhancement of 50-65% being observed at 0.2% ethanol concentration. In contrast, the addition of ethanol in vitro to hepatic and kidney membranes derived from rats chronically exposed to ethanol in vivo did not affect BE binding. Our findings demonstrate that chronic alcohol exposure lowers immunoreactive BE in plasma and reduces BE binding in hepatic and kidney membranes. The observed reduction of BE binding may be due to ethanol-induced changes in membrane composition.
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PMID:Chronic ethanol treatment decreases specific nonopiate beta-endorphin binding to hepatic and kidney membranes and lowers plasma beta-endorphin in the rat. 294 Sep 36

The purpose of the present study was to investigate the effects of activation of different second messenger systems on protein phosphorylation in pituitary corticotrophic tumor cells (AtT-20/D16-16). Using two-dimensional gel analysis of cytosolic extracts from AtT-20 cells, several phosphoproteins exhibited alterations in 32P incorporation in response to stimulation of the cells with either forskolin--an activator of adenylate cyclase--or 12-O-tetradecanoyl phorbol-13-acetate (TPA)--a tumor promoting phorbol ester linked to protein kinase C activation. Alterations in phosphorylation levels were seen for phosphoproteins of the following apparent molecular weights and pIs: 87 kDa (pI 4.4-4.6), 67 kDa (pI 4.7-4.9), 43 kDa (pI 4.8-5.0), 39 kDa (pI 4.9-5.1), 33 kDa (pI 4.8-5.0), 19.5 kDa (pI 5.7-5.9), 19 kDa (pI 5.8-6.0), 16 kDa (pI 5.2-5.4) and 14 kDa (pI 5.1-5.3). For individual phosphoproteins, 32P incorporation varied over time and was also modulated by concentrations of Ca2+ and Mg2+ in the incubation medium. Treatment of the cells with forskolin led to statistically significant changes in the phosphorylation states of the 19.5 and 14 kDa proteins. Treatment of the cells with TPA also produced statistically significant changes in the 19.5 and 14 kDa proteins but, in addition, the 87 kDa, the 39 kDa and the 16 kDa phosphoproteins also exhibited significant changes. Alterations in the phosphorylation states of the 19.5 and the 14 kDa proteins were significantly correlated with alterations in beta-endorphin release from the cells. The primary finding of the present study was that activation of distinct second messenger systems can lead to alterations in the phosphorylation states of both shared and distinct phosphoproteins.
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PMID:Activation of distinct second messenger systems in anterior pituitary corticotrophic tumor cells alters the phosphorylation states of both shared and distinct cytosolic proteins. 295 57

The effects of dopamine on proopiomelanocortin (POMC) gene expression were compared in primary cultures of the anterior and intermediate lobes of the rat pituitary. A single-stranded POMC complementary DNA was used to quantitate POMC messenger RNA levels. Treatment with dopamine (1 microM) for 48 h reduced POMC messenger RNA levels in the intermediate lobe by 77%, but had no effect on POMC gene expression in the anterior lobe. Dopamine D2 receptors were implicated in the response, as bromocriptine (100 nM). reproduced the dopamine inhibition. The responses to dopamine and bromocriptine were antagonized by haloperidol (10 microM). The decrease in POMC messenger RNA levels was dose dependent with ED50 values of about 50 and 0.1 nM for dopamine and bromocriptine, respectively. The accumulation of POMC-derived peptides, beta-endorphin and alpha-melanocyte-stimulating hormone, over 2 days was measured by radioimmunoassay and was shown to parallel the changes in POMC synthesis. The dopamine-induced inhibition of intermediate lobe POMC synthesis was unaffected by isoprenalin (5 microM) and corticotropin-releasing factor (10 nM), although these treatments had stimulatory effects when tested alone. Activating adenylate cyclase with forskolin (1 microM) or treatment with 8-bromocyclic adenosine monophosphate (1 mM) doubled POMC messenger RNA levels, and, when tested against these stimuli, bromocriptine still produced a 30% inhibition of POMC gene expression. These observations suggest that D2 receptor induced inhibition of POMC gene expression is not only mediated by a decrease in cyclic adenosine monophosphate levels. When cells were pretreated with pertussis toxin (100 ng/ml), the bromocriptine-induced inhibition was almost completely lost, suggesting that the dopaminergic inhibition is mediated by guanosine triphosphate binding proteins.
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PMID:Dopamine inhibition of proopiomelanocortin gene expression in the intermediate lobe of the pituitary. Interactions with corticotropin-releasing factor and the beta-adrenergic receptors and the adenylate cyclase system. 296 67

Muscarinic receptor activation on the AtT-20 clonal line of mouse pituitary corticotrophs, inhibits forskolin-stimulated cyclic AMP formation and adrenocorticotropin secretion. In this study, the effect of prolonged receptor stimulation with the muscarinic agonist oxotremorine was found to reduce, in a time-dependent manner, the ability of oxotremorine to inhibit the AtT-20 cell response to forskolin. Pretreatment with oxotremorine also reduced the density of muscarinic receptors without affecting the affinity of these sites for [3H]quinuclidinyl benzilate. In addition to desensitizing the muscarinic receptor, oxotremorine pretreatment also enhanced the ability of forskolin to stimulate cyclic AMP formation and adrenocorticotropin secretion. The apparent sensitizing effect on cyclic AMP synthesis, extended to other muscarinic agents as well as other secretory agonists, was dependent on the oxotremorine concentration used during pretreatment and required at least 2 hr of pretreatment. Enhancement of forskolin-stimulated cyclic AMP accumulation by oxotremorine pretreatment was blocked by cycloheximide and reversed by the muscarinic antagonist, (-)-scopolamine, or by a 5-hr recovery period after pretreatment. The data suggest that prolonged muscarinic receptor activation (rather than simple occupancy) leads to an enhancement of adenylate cyclase activity in AtT-20 cells; whether this effect is coupled to the progressive loss of the inhibitory function of the muscarinic receptor and the receptor down-regulation is unknown.
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PMID:Muscarinic cholinergic receptors in mouse pituitary tumor cells: prolonged agonist pretreatment decreases receptor content and increases forskolin- and hormone-stimulated cyclic AMP synthesis and adrenocorticotropin secretion. 298 17

Whether peptide hormones other than ACTH may be responsible for the difference in size or rate and pattern of steroidogenesis of the fetal zone (FZ) compared to those of the neocortex (NC) of the human fetal adrenal gland is controversial. In the present investigation, the activity of adenylate cyclase in membrane fractions of separated zones of the human fetal adrenal gland was determined. Basal adenylate cyclase activity was 2- to 3-fold greater in NC than in FZ membrane fractions. The addition of ACTH-(1-24) stimulated adenylate cyclase activity in both zones, but the activity was more sensitive to ACTH (10(-10) M) in NC fractions than in FZ fractions (10(-7) M). In addition to ACTH-(1-24), the effect of other ACTH-related peptides on the activity of adenylate cyclase in the separated zones of the adrenal gland was investigated. 16K fragments 2-36, gamma 3MSH, alpha MSH, beta-endorphin, leu-enkephalin, and met-enkephalin, as well as hCG, FSH, prostaglandin E2, prostaglandin F2 alpha, epinephrine, and norepinephrine did not stimulate adenylate cyclase activity in either zone. It is concluded that basal and ACTH-(1-24)-stimulated adenylate cyclase activities are greater in NC than in FZ membrane fractions. In addition, the results of the present investigation do not support the concept that other ACTH-related peptides or peptide or protein hormones increase steroidogenesis by stimulating adenylate cyclase activity in the human fetal adrenal gland.
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PMID:Adenylate cyclase activity in neocortex and fetal zone membrane fractions of the human fetal adrenal gland. 298 5

Continuous treatment (1-3 weeks) with imipramine or adrenocorticotropin (ACTH) decreases the responsiveness of the norepinephrine-coupled cyclic nucleotide generating system in rat brain cerebral cortex. Experiments were undertaken to determine which component of the second messenger system is influenced by the hormone and antidepressant. Neither treatment modified the amount or function of extractable stimulatory guanine nucleotide binding protein or the activities of adenylate cyclase or phosphodiesterase. While both imipramine and ACTH treatment decreased the cyclic AMP response to norepinephrine, only imipramine administration influenced the response to isoproterenol. ACTH treatment was found to reduce the alpha adrenergic potentiation of isoproterenol- and 2-chloroadenosine-stimulated cyclic AMP production, as well as reduce the sensitivity of the norepinephrine response to prazosin. These findings indicate that imipramine and ACTH treatments decrease the responsiveness of the rat brain norepinephrine-stimulated cyclic AMP generating system through actions on the alpha and beta adrenergic receptor components. The results suggest that noradrenergic receptor activity may be under the control of adrenal and/or pituitary hormones.
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PMID:Effect of imipramine and adrenocorticotropin administration on the rat brain norepinephrine-coupled cyclic nucleotide generating system: alterations in alpha and beta adrenergic components. 299 1

alpha-Melanotropin (alpha-melanocyte stimulating hormone, alpha-MSH) stimulates tyrosinase activity in Cloudman S91 murine melanoma cells. Three [Nle4, D-Phe7]-substituted alpha-melanotropin analogues, [Nle4, D-Phe7]-alpha-MSH, Ac-[Nle4, D-Phe7]-alpha-MSH4-11-NH2, and Ac-[Nle4, D-Phe7]-alpha-MSH4-10-NH2, are at least 100-fold more effective than alpha-MSH in stimulating melanoma tyrosinase, the rate-limiting enzyme in melanin biosynthesis. These [Nle4, D-Phe7]-substituted melanotropin analogues induce tyrosinase activity in melanoma cells with shorter contact times than required by the native hormone, alpha-MSH. [Nle4, D-Phe7]-substituted melanotropins also induce a prolonged (residual) stimulation of melanoma tyrosinase. Following incubation of melanoma cells in the presence of [Nle4, D-Phe7]-alpha-MSH for 24 h, tyrosinase activity is maintained for up to 6 days in the absence of the melanotropin. The shorter 4-10 and 4-11 fragment analogues also exhibit residual melanotropic activity. The prolonged stimulation of tyrosinase in the absence of the analogues is maintained even though melanoma cells continue to divide about every 24 h. These results suggest that melanoma cells possess spare melanotropin receptors and that [Nle4, D-Phe7]-substituted analogues bind almost irreversibly to these receptors or to some other component of the adenylate cyclase enzyme complex responsible for enhancing tyrosinase activity and melanin production.
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PMID:Prolonged stimulation of S91 melanoma tyrosinase by [Nle4, D-Phe7]-substituted alpha-melanotropins. 299 67

With the use of [125I]acetyl human beta-endorphin (Ac-hBE), specific binding sites for beta-endorphin (BE) were identified in the liver, kidney, adrenal, spleen, and testis of adult male rats, whereas specific BE-binding sites were not present in the ventral prostate or pancreas. In those tissues containing specific BE-binding sites, microsomal membranes (15,000-100,000 X g pellet) exhibited higher BE-binding capacity than the crude homogenate (125-100,000 X g pellet). The binding of BE was saturable, and maximal, specific binding was achieved with a 60-min incubation at 22 C. Furthermore, optimal BE binding was dependent on the presence of magnesium chloride. Scatchard analysis of BE binding to hepatic membranes revealed the existence of two classes of binding sites. One class had an apparent Ka of 0.019 X 10(9) M-1 and a lower number of binding sites (9.1 pmol BE/mg protein), whereas the other class had a lower affinity (apparent Ka of 0.0006 X 10(9) M-1) and a higher number of binding sites (159 pmol/mg protein). Specific BE binding to hepatic membranes was inhibited (80-100%) by rat AcBE-(1-27) and -(1-31), nonacetylated rat BE-(1-31), and human beta-lipotropin. At substantially higher peptide concentrations (greater than 10(-5) M), gamma-endorphin, met-enkephalin, or leu-enkephalin inhibited BE binding by 20-40%. In addition, opiate receptor-binding drugs, such as morphine and naloxone, at 10(-5) M did not alter BE binding to hepatic membranes. Incubation of hepatic membranes with BE induced a dose-related increase in membrane adenylate cyclase activity, and 0.5 X 10(-10) M BE resulted in a maximal enhancement of adenylate cyclase activity to 148% above control values. Water-deprived or salt-loaded male rats with chronically lowered immunoreactive plasma BE exhibited substantially increased BE binding to adrenal and kidney tissue. Specific binding sites for BE occur in a variety of peripheral tissues, and alterations of circulating BE result in changes in the capacity of certain peripheral tissues to bind BE. Finally, occupancy of specific BE-binding sites in peripheral tissue stimulates the adenylate cyclase-cAMP system, which suggests that the peripheral actions of circulating BE may be mediated via this system.
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PMID:Evidence that beta-endorphin binds to specific receptors in rat peripheral tissues and stimulates the adenylate cyclase-adenosine 3',5'-monophosphate system. 299 12

Corticotropin-releasing factor (CRF) is the most potent and effective natural stimulant of corticotropin (ACTH) secretion. In a tumor cell line of the mouse anterior pituitary (AtT-20/D16-16) consisting of a homogeneous population of corticotrophs, CRF is known to increase adenylate cyclase and cAMP-dependent protein kinase activities as well as to release ACTH. To determine whether activation of cAMP-dependent protein kinase is essential for CRF to evoke the secretion of ACTH, an inhibitor (PKI) of this kinase was inserted into AtT-20 cells. This was accomplished by first encapsulating PKI into liposomes and then covalently coupling them to protein A for binding to antibodies directed against an AtT-20 cell surface antigen, N-CAM (neural cell adhesion molecule). The binding of the liposomes to the anti-N-CAM antibodies led to the internalization of the PKI into the tumor cells. The PKI treatment greatly attenuated CRF-stimulated ACTH release as well as the secretory response to beta-adrenergic agonists. However, ACTH release in response to caerulein, an agonist of cholecystokinin 8 receptors, was not altered by the PKI treatment. CRF treatment also increased the levels of mRNA for proopiomelanocortin (POMC), the precursor for ACTH in AtT-20 cells. Application of liposomes containing PKI to AtT-20 cells blocked the ability of CRF and 8-bromo-cAMP, but not phorbol ester, to increase POMC mRNA levels. The results revealed an essential role for cAMP in mediating the effect of CRF on ACTH release and POMC gene expression.
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PMID:Corticotropin-releasing factor-induced adrenocorticotropin hormone release and synthesis is blocked by incorporation of the inhibitor of cyclic AMP-dependent protein kinase into anterior pituitary tumor cells by liposomes. 299 99


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