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)

alpha-MSH was found to decrease the recently characterized dopachrome tautomerase activity in cultures of B16/F10 mouse melanoma cells. Other stimulating agents of melanogenesis, like dibutyryl cyclic AMP, 3-isobutyl-1-methylxanthine, theophylline, retinol, and retinoic acid, caused the same effect. The grade of inhibition depended on the nature of the agent and the time of exposure. In all cases, both melanin production and tyrosinase activity were activated by these treatments, although the grade of tyrosine hydroxylase and dopa oxidase stimulation was different. Moreover, no correlation among the intensities of dopachrome tautomerase inhibition and tyrosinase activation by the tested agents could be obtained. The significance of these results in the regulation of mammalian melanogenesis is discussed.
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PMID:Alpha-MSH and other melanogenic activators mediate opposite effects on tyrosinase and dopachrome tautomerase in B16/F10 mouse melanoma cells. 132 99

Exposure of adrenal Y-1 cells to C2 toxin results in an increase in steroid release that is accompanied by a rounding of the cell. The actions of C2 toxin mimic those of adrenocorticotropin and cholera toxin except that there is no increase in intracellular cyclic AMP content. In the present study we provide evidence that C2 toxin increases steroid output from Y-1 cells through an alteration in the microfilament network of the cell. C2 toxin significantly increased steroid output after 3 hr of exposure. This effect was accompanied by a significant increase in the transport of [3H]cholesterol to the mitochondrial fraction, independent of cholesterol uptake by the cell. The toxin was unable to increase steroid output from cells prerounded in suspension culture. The protease inhibitors benzamidine and phenylmethylsulfonyl fluoride did not attenuate the ability of C2 toxin to alter the morphology of Y-1 cells. A 3-hr exposure to C2 toxin resulted in the ADP-ribosylation of 50 to 60% of the total actin pool. Fluorescein isothiocyanate-labeled phalloidin visualization of the cytoskeleton of toxin-treated cells confirmed that the toxin caused a decrease in the stress fiber network. C2 toxin treatment of a protein kinase A mutant Y-1 cell (Kin 8) resulted in morphological changes and an increase in steroid output that was not different from that observed for wild type Y-1 cells. The data suggest that C2 toxin increases steroid output from adrenal Y-1 cells by a cyclic AMP-independent mechanism that involves the microfilament network of the cell.
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PMID:Botulinum C2 toxin and steroid production in adrenal Y-1 cells: the role of microfilaments in the toxin-induced increase in steroid release. 137 Nov 60

Calcitonin gene-related polypeptide (CGRP) was purified from ovine hypothalamic extracts. Its amino acid sequence was determined as: Ser-(Cys)-Asn-Thr-Ala-Thr-(Cys)-Val-Thr-His-Arg-Leu-Ala-Gly-Leu-Leu-Ser- Arg-Ser - Gly-Gly-Val-Val-Lys-Ser-Asn-Phe-Val-Pro-Thr-Asn-Val-Gly-Ser-Gln-Ala-Phe- NH2. This sequence differs from rat CGRP by two amino acid substitutions (Ser for Asp25 and Gln for Glu35). Adenylate cyclase stimulating activity in rat pituitary cell cultures was monitored during the isolation. CGRP had adenylate cyclase stimulating activity comparable to corticotropin-releasing hormone, suggesting a hypophysiotropic role for CGRP. This is the first chemical characterization of CGRP in the brain (hypothalamus).
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PMID:Identification of calcitonin gene related peptide in ovine hypothalamic extract. 141 24

Relatively little is known about the regulation of secretion of hypothalamic beta-endorphin, the potent opioid that is believed to play a variety of physiological roles in brain. Previous work has shown that arginine vasopressin (AVP), which acts in brain primarily via activation of the phosphoinositol (PI) second messenger system, stimulates secretion of hypothalamic beta-endorphin. To test the hypothesis that activators of protein kinase C (PKC), which is activated following PI hydrolysis, stimulates secretion of beta-endorphins from hypothalamus, we studied the separate effects of stimulators of PKC including phorbol ester 12-myristate-13-acetate (PMA) and 1-oleolyl-2-acetyl glycerol (OAG- a diacyl glycerol analogue) on secretion of immunoreactive (IR-) beta-endorphin (measured by RIA) from dissociated fetal rat hypothalamic cell cultures. We also studied AVP and angiotensin II (Ang II), hypothalamic peptides which activate the PI second messenger pathway, and interactions of PMA and forskolin (FSK), an activator of the cyclic AMP/protein kinase A (PKA) pathway. PMA, OAG, AVP, and Ang II stimulated IR-beta-endorphin secretion. The stimulatory effect of both PMA and FSK on IR-beta-endorphin secretion was greater than that of PMA or FSK alone and was essentially additive.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protein kinase C activators stimulate beta-endorphin secretion from hypothalamic cells. 142 53

Previous work from our laboratory has shown that both cyclic AMP and calcium/calmodulin appear to be involved in the regulation of melanogenesis in murine B16 melanoma cells. In these cells as in murine Cloudman S91 cells, melanogenic responsiveness to melanocyte-stimulating hormone (MSH) varies with cell density in culture. Our objective in this study was to learn more about the intracellular systems involved in the control of melanogenesis, particularly the role played by calcium. The melanogenic response to alpha MSH was compared to the response to drugs affecting intracellular free calcium and calmodulin over a range of cell densities in B16F1 cells. alpha MSH-stimulated melanin production was extremely density-dependent but alpha MSH-stimulated cyclic AMP production was independent of cell density. The melanogenic response to agents that increased intracellular calcium (A23187) or inhibited intracellular calmodulin varied with cell density. A drug (TMB8) that lowered intracellular free calcium, however, increased melanogenesis independently of cell density. At high cell density it was found that an elevation in calcium decreased melanogenesis, whereas agents that reduced calcium or inhibited calmodulin activity increased melanogenesis. At low cell density, however, the inhibitory response to A23187 was lost and in some experiments even stimulated melanogenesis. These data suggest that the calcium/calmodulin signalling system has an inhibitory influence on melanogenesis, and its expression, which depends upon cell density, may also modulate the response to stimulatory agents such as alpha MSH.
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PMID:Evidence for a calcium/calmodulin involvement in density-dependent melanogenesis in murine B16 melanoma cells. 166 9

Alpha-MSH, considered an important pigmentation hormone, binds to melanocytes and is thought to stimulate melanogenesis through a cyclic-AMP-dependent mechanism. The binding of alpha-MSH to follicular melanocytes has been investigated in human hair of different colors, ranging from black to blond and senile white. Hairs were plucked, the follicles were cut off, and an alpha-MSH binding assay, using a radiolabeled alpha-MSH analogue, was performed on these bulbs. As controls of each assay, fragments of hairs of the same person were used. The results show a dose-response relationship and the assay seems to be specific for alpha-MSH, because other peptides such as ACTH, beta-LPH and beta-endorphins do not compete for binding sites as alpha-MSH does. These binding sites seem to be present only on melanin synthesizing melanocytes, since the controls and follicles of senile white hair, which do not contain active melanocytes, show negative results. All the assays were performed on raw material, i.e., whole plucked hair follicles. This is the first time that binding sites for alpha-MSH have been demonstrated on human scalp hair follicles. In addition, their presence was found to be associated with active melanin production; their absence was demonstrated on senile white hair follicles.
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PMID:Evidence for alpha-MSH binding sites on human scalp hair follicles: preliminary results. 166 22

Long-term regulation of mammalian steroid hormone synthesis occurs principally by transcriptional regulation of the gene for the rate-limiting cholesterol side-chain cleavage enzyme P450scc. Adrenal steroidogenesis is regulated primarily by two hormones: adrenocorticotropin, which works via cyclic AMP (cAMP) and protein kinase A, and angiotensin II, which works via Ca2+ and protein kinase C. Forskolin and 8-bromo-cAMP stimulated, while prolonged treatment with a phorbol ester (12-O-tetradecanoylphorbol-13-acetate [TPA]) and a calcium ionophore (A23187) additively suppressed accumulation of endogenous P450scc mRNA in transformed murine adrenal Y1 cells. In Y1 cells transfected with 2,327 base pairs of the human P450scc promoter fused to the bacterial gene for chloramphenicol acetyltransferase (CAT), forskolin increased CAT activity 900% while combined TPA plus A23187 reduced CAT activity to 15% of the control level. Forskolin induced the P450scc promoter as rapidly as a promoter containing two cAMP-responsive elements fused to a simian virus 40 promoter, a system known to respond directly to cAMP. Basal expression was increased by sequences between -89 and -152 and was increased further by sequences between -605 and -2327. This upstream region also conferred inducibility by cAMP. TPA plus A23187 transiently increased CAT activity before repressing it, reflecting the complex actions of angiotensin II in vivo. Repression by prolonged treatment with TPA plus A23187 was mediated by multiple elements between -89 and -343. Induction of CAT activity by forskolin was not diminished by treatment with TPA plus A23187, nor were the regions of the promoter responsible for regulation by the two pathways coisolated. Thus, the human gene for P450scc is repressed by TPA plus A23187 by mechanisms and sequences independent of those that mediate induction by cAMP.
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PMID:Human P450scc gene transcription is induced by cyclic AMP and repressed by 12-O-tetradecanoylphorbol-13-acetate and A23187 through independent cis elements. 170 Feb 77

Mouse melanoma cells in culture respond to melanocyte-stimulating hormone (MSH) or to cyclic AMP analogues by demonstrating an increase in tyrosinase activity. In this study the effect of the tumor promoter, 12-O-tetradecanoylphorbol 13-acetate (TPA), on the hormonal induction of tyrosinase was examined. TPA was found to lower basal levels of tyrosinase activity in melanoma cells and to reduce tyrosinase levels in cells treated with either MSH (10(-7) M), dibutyryl cAMP (10(-4) M), isobutylmethylxanthine (IBMX, 10(-4) M), or with the potent MSH analogue, [Nle4,D-phe7]-alpha-MSH. The phorbol ester, phorbol 12,13-dibutyrate was also effective in lowering tyrosinase activity levels, while 4 alpha-phorbol 12,13-didecanoate, which does not bind protein kinase C, was ineffective. In order to determine how TPA may reduce tyrosinase activity in melanoma cells, the levels of tyrosinase mRNA in untreated or TPA-treated cells were determined by Northern blot analysis. A marked down-regulation of constitutive levels of tyrosinase mRNA was observed in cells treated with the tumor promoter. Tyrosinase mRNA levels in cultures exposed to TPA for 48 h were only 7% of control levels. Tyrosinase mRNA levels in cells treated with both MSH and TPA were also lower than in cells treated with MSH alone. Previous studies from this laboratory have shown that insulin both lowers basal tyrosinase activity in melanoma cells and antagonizes the MSH stimulation of the enzyme. We have now determined that this inhibition is also due to reduced levels of tyrosinase mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Down-regulation of tyrosinase mRNA levels in melanoma cells by tumor promoters and by insulin. 170 21

The Ca2(+)-mobilizing hormone angiotensin II (AII) dose-dependently inhibited the K(+)-induced sustained increase of cytoplasmic Ca2+ concentration in adrenal glomerulosa cells and caused a rapid decrease of cytoplasmic Ca2+ when added to cells already stimulated with K+. These effects of AII on the K(+)-induced Ca2+ signal were mimicked, although less effectively, by other Ca2(+)-mobilizing agonists such as [Arg8]vasopressin (AVP) and thapsigargin. Phorbol esters did not show such effects, nor did corticotropin (ACTH), a secretagogue acting via cyclic AMP. The K(+)-stimulated initial 45Ca2+ uptake, a measure of Ca2+ entry into glomerulosa cells, was also prevented by AII pretreatment, and was inhibited by AVP, but not by ACTH. The stimulatory effect of K+ on aldosterone production, however, was not inhibited by AII, and the AII-induced aldosterone production was further increased by increasing K+. These data indicate that AII is able to inhibit static increases in cytoplasmic Ca2+ by inhibiting Ca2+ entry through voltage-sensitive Ca2+ channels and, possibly, by activating Ca2+ extrusion from the cells. It is also concluded that the Ca2+ signal evoked by AII is very efficient in stimulating hormone secretion, and the secretory response of the cells becomes more sensitive to any further increase of Ca2+ entry through voltage-sensitive Ca2+ channels.
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PMID:Angiotensin II inhibits K(+)-induced Ca2+ signal generation in rat adrenal glomerulosa cells. 184 39

Both angiotensin II and adrenocorticotropic hormone (ACTH) are well known to play a crucial role on the regulation of aldosterone production in adrenal glomerulosa cells. Recent observations suggest that the steroidogenic action of ACTH is mediated via the cAMP messenger system, whereas angiotensin II acts mainly through the phosphoinositide pathway. However, there have been no reports concerning the interaction between the cAMP messenger system activated by ACTH and the Ca2+ messenger system induced by angiotensin II. Both ACTH and angiotensin II simultaneously act on adrenal cells for regulating steroidogenesis under physiological conditions. Thus the present experiments were performed to examine the effect of ACTH on the action of angiotensin II by measuring angiotensin II receptor activity, cytosolic Ca2+ movement, and aldosterone production. The major findings of the present study are that short-term exposure to a high dose of ACTH (10(-7) M) inhibited 125I-angiotensin II binding to bovine adrenal glomerulosa cells, decreased the initial spike phase of [Ca2+]i induced by angiotensin II, and inhibition of angiotensin II-induced aldosterone production. Low dose of ACTH (10(-10) M), which did not increase cAMP formation, did not affect angiotensin II receptor activity. These studies have shown that angiotensin II receptors of bovine adrenal glomerulosa cells can be down-regulated by 1 mM dibutyryl cyclic AMP, as well as by effectors which are able to activate cAMP formation (10(-7) M ACTH and 10(-5) M forskolin). The rapid decrease in angiotensin II receptors induced by 10(-7)M ACTH was associated with a decreased steroidogenic responsiveness and a decreased rise in the [Ca2+]i response induced by angiotensin II. These studies show that the cAMP-dependent processes activated by ACTH have the capacity to interfere with signal transduction mechanisms initiated by receptors for angiotensin II.
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PMID:ACTH-induced inhibition of the action of angiotensin II in bovine zona glomerulosa cells. A modulatory effect of cyclic AMP on the angiotensin II receptor. 184 18


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