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Query: UNIPROT:P01189 (beta-endorphin)
21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have evaluated the role of calcium in basal and secretagogue-stimulated release of beta-endorphin and PRL and the levels of their respective mRNAs in primary cultured rat anterior pituitary cells. Treatment of anterior pituitary cells with the calcium channel blocker methoxyverapamil (D600; 10 microM) or with calcium-free medium for 1 h did not alter the basal release of beta-endorphin and only partially blocked CRF (10 nM)-stimulated beta-endorphin release. In contrast to these effects of D600 or calcium-free medium on corticotrophs, both of these test conditions decreased basal secretion of PRL from lactotrophs by 50-70% and completely blocked forskolin (10 microM)-stimulated PRL secretion. Although omission of calcium from the culture medium caused a 50% decrease in basal levels of both proopiomelanocortin (POMC) and PRL mRNA, treatment of cells with D600 did not significantly alter the basal levels of POMC or PRL mRNA. Treatment of cells with D600 partially blocked CRF-stimulated elevation of POMC mRNA and forskolin-stimulated elevation of PRL mRNA. The calcium agonist barium (1 mM) produced a 2-fold increase in both beta-endorphin and PRL release, which was blocked by D600. Treatment of cells with barium had no effect on POMC mRNA levels, but increased PRL mRNA levels. D600 treatment of cells partially blocked barium-stimulated PRL mRNA levels. These findings demonstrate a calcium-dependent as well as a calcium-independent component of CRF-stimulated beta-endorphin secretion and CRF-stimulated POMC mRNA elevation. In contrast, PRL secretion and biosynthesis appear to be totally calcium-dependent processes.
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PMID:Calcium-independent and calcium-dependent mechanisms regulate corticotropin-releasing factor-stimulated proopiomelanocortin peptide secretion and messenger ribonucleic acid production. 349 Sep 63

Arginine-vasopressin (AVP) stimulates adrenocorticotropin and beta-endorphin release from corticotrophs of the anterior pituitary gland through mechanisms which are not initiated by an elevation of the cellular levels of adenosine-3',5'-cyclic-monophosphate. In the present study the effect of AVP on the cytoplasmic concentrations of free calcium ions in rat anterior pituitary cells was examined. Cytosolic free Ca2+ concentrations were monitored directly using the new, intracellularly trapped fluorescent indicator fura-2. In cells incubated in medium containing 1.3 mmol/l Ca2+, AVP (100 nmol/l) caused an immediate elevation of the cytoplasmic Ca2+ concentration by about 50 nmol/l (P less than 0.001). The intracellular Ca2+ levels remained elevated during the observation period of 2-3 min. This effect of AVP was blocked by a specific vasopressin antagonist. By contrast, the glucocorticoid dexamethasone did not affect the AVP-induced elevation of cytosolic Ca2+ concentration. When the cells were incubated in Ca2+-free medium (Ca2+ omitted, EGTA 2 mmol/l), the AVP-induced as well as the K+ depolarization-induced increase in free cytoplasmic Ca2+ were abolished, whereas the ionophore ionomycin evoked a rapid transient elevation of free Ca2+. The increase in cytoplasmic Ca2+ concentration induced by AVP was preserved in medium containing the calcium channel blockers Mg2+ (Mg2+ 31.2 mmol/l; Ca2+ 1.3 mmol/l) or nifedipine (1 mumol/l). The potassium-evoked calcium signal was blocked by Mg2+ (31.2 mmol/l). We conclude that vasopressin induces a rapid rise in the cytoplasmic concentration of free calcium ions in corticotrophs. Vasopressin may mobilize calcium through mechanisms that neither are glucocorticoid-sensitive nor involve the influx of extracellular calcium through voltage-dependent calcium channels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intracellular free calcium concentration in rat anterior pituitary cells as indicated by fura-2: effect of arginine-vasopressin. 368 98

The effects of forskolin, an adenylate cyclase activator, were investigated on adrenocorticotropin (ACTH) secretion from AtT-20/ D16 -16 mouse pituitary tumor cells. Forskolin increased adenylate cyclase activity in these cells in the absence of added guanyl nucleotide, an effect blocked by somatostatin. Cyclic AMP synthesis and ACTH secretion increased in a concentration-dependent manner, not only in the clonal cells, but in primary cultures of rat anterior pituitary as well. Somatostatin inhibited cyclic AMP synthesis and ACTH secretion in response to forskolin. When forskolin was coapplied with corticotropin releasing factor, cyclic AMP synthesis was potentiated and ACTH secretion additive. The calcium channel blocker, nifedipine, inhibited forskolin, and 8-bromocyclic AMP stimulated ACTH secretion. These data suggest that ACTH secretion may be regulated at the molecular level by changes in cyclic AMP formation, which in turn regulate a calcium gating mechanism.
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PMID:Forskolin stimulates adenylate cyclase activity, cyclic AMP accumulation, and adrenocorticotropin secretion from mouse anterior pituitary tumor cells. 614 27

Freshly isolated rat lymphocytes were tested for corticotropin (ACTH)-dependent calcium uptake. Physiological levels of corticotropin (0.01-1 nM) were found to stimulate both an uptake of 45Ca2+ and a rise in cAMP. The calcium uptake was delayed by 2 min after ACTH addition, but was rapid and transient after the onset of uptake. The extent of calcium uptake was dose dependent on the corticotropin concentration and reached a maximum by 1 nM. Several fragments of corticotropin were tested for activity; both full-length 1-39 and a functional truncated form, 1-25, had equivalent effects on 45Ca influx at 1 nM; however, alpha MSH-(1-13), ACTH-(11-24), or a mixture of alpha MSH and ACTH-(11-24) had no effect on 45Ca influx. Extracellular calcium uptake was blocked by the calcium channel blockers lanthanum, diltiazem, nifedipine, and omega-conotoxin. Splenic lymphocytes that express ACTH receptors had ligand-dependent calcium uptake, but thymocytes that lack ACTH receptors had no ligand-dependent calcium uptake. A mouse adrenal cell line, Y-1, showed the same 45Ca uptake kinetics. These findings demonstrate that both lymphocytes and adrenal cells have a functional ACTH-dependent calcium uptake mechanism.
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PMID:Adrenocorticotropic hormone stimulates a transient calcium uptake in rat lymphocytes. 795 1

The influx of extracellular calcium is a critical step involved in the stimulated release of adrenocorticotropin (ACTH) from pituitary corticotrophs. It has been proposed that the mechanism of early glucocorticoid feedback is mediated through inhibition of stimulus-evoked calcium transients. We tested this hypothesis using corticotrophic mouse pituitary AtT-20 cells by coevaluating secretory dynamics and cytosolic calcium transients. In static monolayer culture and in a dynamic microperifusion system, dexamethasone (DEX, 100 nM, 2 h) significantly inhibited ACTH secretion stimulated by corticotropin-releasing hormone (CRH, 100 nM). When ACTH was stimulated by KCl (56 mM) depolarization or the voltage-dependent calcium channel agonist, maitotoxin (MTX, 1 ng/ml), DEX did not inhibit secretion. In contrast, CRH-, KCl-, and MTX-stimulated ACTH secretion were significantly inhibited in static monolayer culture when cells were pretreated with the voltage-dependent calcium channel blocker, nifedipine (NIF, 1 microM, 15 min), confirming the requirement for the influx of extracellular calcium. Intracellular calcium was measured under similar culture conditions in populations of cells grown on coverslips, utilizing the fluorescent calcium indicator, fura-2. DEX had no effect on basal, spike, or plateau calcium levels in response to CRH, KCl or MTX stimulation. For example, CRH stimulation resulted in an increase in intracellular calcium from a basal concentration of 90 +/- 3.1 nM (mean +/- SE) to a plateau of 222 +/- 8.7 nM, whereas the plateau after DEX was 225 +/- 4.1 nM. In contrast, NIF significantly lowered the stimulated calcium response to each secretagogue (spike and plateau). These results do not support the hypothesis that glucocorticoids suppress stimulated secretion of ACTH from corticotrophs through an effect on intracellular calcium transients. Instead, the data suggest that early glucocorticoid negative feedback occurs at a step(s) distal to the influx of extracellular calcium.
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PMID:Glucocorticoids do not affect intracellular calcium transients in corticotrophs: evidence supporting an effect distal to calcium influx. 796 85

Early glucocorticoid feedback in sheep anterior pituitary (AP) cells was compared and contrasted with that in mouse pituitary tumor AtT-20 cells. Dexamethasone (DEX) inhibited corticotropin-releasing hormone (CRH)-stimulated adrenocorticotropin (ACTH) release in a concentration- and time-dependent manner with similar potency amongst cell types. This inhibition was mediated through type II glucocorticoid receptors and required the synthesis of new protein. However, stimulation of protein kinase C with phorbol 12-myristate 13-acetate (PMA) resulted in greater ACTH release and greater inhibition by DEX in sheep AP cells. In contrast to sheep AP cells, AtT-20 cells were insensitive to glucocorticoids when secretion was stimulated by KCl depolarization or the voltage-dependent calcium channel agonist, maitotoxin (MTX). In both cell types, CRH-, KCl-, and MTX-stimulated ACTH release was inhibited by the calcium channel blocker, nifedipine (NIF). Whereas NIF also inhibited PMA-induced ACTH secretion in AtT-20 cells, it did not in sheep AP cells. These data demonstrate that early glucocorticoid feedback is operative in sheep corticotrophs and that AtT-20 cells appear to serve as an appropriate mechanistic model for aspects of negative feedback when the CRH-protein kinase A pathway is activated but may not be appropriate when ACTH secretion is activated via other intracellular signaling pathways.
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PMID:Glucocorticoid negative feedback in sheep corticotrophs: a comparison with AtT-20 corticotroph tumor cells. 806 55

To learn more of the role of calcium in the regulation of melanogenesis, we have used direct manipulation of medium calcium and pharmacological modulation of intracellular calcium to examine the consequences on unstimulated and cyclic AMP elevated tyrosinase activity and melanin synthesis and distribution in B16 melanoma cells. In unstimulated cells, calcium is clearly inhibitory to tyrosinase activity. However, in cells stimulated with cAMP-elevating agents the requirement for extracellular calcium was changed such that cells required a minimum of 0.4-0.6 mmol medium calcium for maximum tyrosinase response to these agents. Paradoxically, pharmacologically increasing intracellular calcium in cAMP-stimulated cells with ionophore inhibited tyrosinase activity, and the calcium-lowering agent TMB8 and the calcium channel blocker verapamil both stimulated tyrosinase activity. When melanin synthesis was measured in cAMP-stimulated cells, TMB8 was found to significantly increase the sensitivity and the maximum melanogenic response to alpha-MSH, suggesting the presence of at least one level of endogenous calcium inhibitory control operative in these cells. In addition, TMB8 changed the distribution of melanin between the cell and the medium such that, in the presence of alpha-MSH and TMB8, significantly more melanin was secreted into the medium. These data suggest that calcium is required for several steps in melanogenesis, having an apparently inhibitory effect on pre-tyrosinase activity in unstimulated cells, but also showing evidence of a positive role in cyclic AMP-stimulated tyrosinase activity, as well as a further possible inhibitory role in melanin movement or secretion.
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PMID:Calcium plays a complex role in the regulation of melanogenesis in murine B16 melanoma cells. 814 88

10(-6) M n-formyl-methionyl-leucyl-phenylalanine (FMLP) stimulated Ca2+ flux in human neutrophils is characterized by a profile composed of two peaks of different amplitude and breadth. beta-Endorphin inhibited the magnitude and modulated the kinetics of the second peak in a manner which was dose-dependent and could reflect either negative cooperativity or heterogeneity of binding sites. The second peak arises from calcium channel activity since in the presence of nifedipine or EGTA it was not evident while the first peak was reduced about 24%. Similarly, at 15 degrees C, where we were unable to detect any channel activity, the first peak was diminished by 35% and beta-endorphin had no detectable effect on this peak. These results led us to conclude that the first peak is chiefly composed of Ca2+ recruited from cytosolic stores which are relatively insensitive to the above treatments and a smaller fraction of calcium originating in calcium channel activity. Hence, we reason that beta-endorphin modulates only the calcium ion flux arising from calcium channel function.
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PMID:Beta-endorphin modulates calcium channel activity in human neutrophils. 830 Aug 59

Corticotropin-releasing factor (CRF) stimulates adrenocorticotropin (ACTH) release via the adenylate cyclase/cAMP-dependent protein kinase system. Because calcium is necessary for receptor-mediated release of ACTH, we have examined the effect of CRF on 45Ca2+ uptake in a corticotroph cell line model, AtT-20. Treatment of AtT-20 cells with CRF (10(-9)-10(-6) M) resulted in dose- and time-dependent increases in 45Ca2+ uptake, up to 2.2-fold above control values. The effect was statistically significant at 1 min and persisted for at least 10 min. Treatment with forskolin (1-30 microM), 8-Br-cAMP (0.5 mM), cholera toxin (CT, 100 ng/ml) and K+ (20 mM) also increased cell-associated 45Ca2+. The effect of K+ was completely blocked by nifedipine (100 microM), whereas the effects of CRF (10(-8) M) were only partially inhibited by this calcium channel antagonist. These data suggested a role of voltage-dependent calcium channels in 45Ca2+ uptake. Short term pretreatment (1-2 h) of AtT-20 cells with CRF (10(-8) M) significantly desensitized both CRF-stimulated cAMP accumulation and ACTH release, but did not attenuate CRF-stimulated 45Ca2+ uptake. Pretreatment with CRF (10(-8) M) for 4 h did not alter CT- or forskolin-stimulated cAMP accumulation and ACTH release. This suggests that the molecular mechanisms of desensitization are proximal to adenylate cyclase. Conversely, long term pretreatment (24 h) of AtT-20 cells with CRF (10(-8) M) induced significant desensitization of CRF-stimulated 45Ca2+ uptake. These results indicate that CRF stimulates calcium uptake in AtT-20 cells via cAMP-dependent and cAMP-independent mechanisms, and that the cellular mechanisms involved in desensitization of cAMP accumulation and ACTH release and those involved in desensitization of calcium uptake are qualitatively different.
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PMID:Corticotropin-releasing factor (CRF) stimulates 45Ca2+ uptake in the mouse corticotroph cell line AtT-20. 838 2

In healthy men, intravenous (IV) endothelin-1 suppresses the growth hormone (GH)-releasing hormone (GHRH)-stimulated increase in GH and prolactin (PRL) and augments corticotropin (ACTH)-releasing factor (CRF)-stimulated secretion of ACTH. Since some actions of endothelin-1 on pituitary function in vitro are antagonized by calcium channel antagonists, we have studied the effect of pretreatment with oral nifedipine (10 mg, given before infusion of endothelin-1 or vehicle) on basal and stimulated concentrations of pituitary hormones in a group of healthy men (N = 6). The augmentative effect of endothelin-1 on CRF-induced ACTH secretion (P < .05) was counteracted by pretreatment with nifedipine. Pretreatment with nifedipine further inhibited (P < .01) the GHRH-induced increase in plasma concentrations of GH (P < .05), which, in keeping with previous data, had already been reduced by IV endothelin-1 alone (P < .05). Thus, both endothelin-1 and nifedipine influence pituitary hormone secretion in healthy man. However, nifedipine does not ubiquitously counteract the effects of endothelin-1 since it enhances some of its actions on the pituitary and diminishes others. Endothelin-1 may therefore influence pituitary function by mechanisms other than activation of calcium channels alone.
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PMID:Effect of endothelin-1 in man--impact on basal and stimulated concentrations of luteinizing hormone, follicle-stimulating hormone, thyrotropin, growth hormone, corticotropin, and prolactin with and without pretreatment with nifedipine. 862 12


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