Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0031511 (pheochromocytoma)
 14,622 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adrenomedullin is a novel hypotensive peptide originally isolated from human pheochromocytoma. Accumulating evidence suggests the possible involvement of adrenomedullin in the physiology of the pulmonary circulation and the pathophysiology of hypoxaemia. The aim of the present study was to investigate the pathophysiological significance of adrenomedullin in hypoxaemia caused by congenital cyanotic heart disease. Subjects were 16 patients with congenital cyanotic heart disease aged 0.8-10 years (Group C) and 12 age-matched control subjects (patients with coronary artery dilatation after Kawasaki disease; Group N). Plasma adrenomedullin concentrations were measured, using radioimmunoassay, in femoral venous, pulmonary arterial and pulmonary venous blood obtained during cardiac catheterization. Plasma adrenomedullin concentrations in Group C were significantly (3-fold) higher than those in Group N at all sampling sites. In Group C, plasma adrenomedullin concentrations in pulmonary venous blood were significantly lower than those in pulmonary arterial blood. Pulmonary uptake of adrenomedullin in Group C was significantly greater than that in Group N. Patients with congenital cyanotic heart disease showed elevated plasma adrenomedullin concentrations and an increased uptake of adrenomedullin in the pulmonary circulation, which may act to dilate pulmonary vessels and increase pulmonary blood flow to alleviate hypoxaemia. Intrinsically increased adrenomedullin levels may function as a compensatory mechanism for hypoxaemia in congenital cyanotic heart disease.
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PMID:Elevated plasma levels of adrenomedullin in congenital cyanotic heart disease. 1033 59

Adrenomedullin (ADM) is a recently discovered peptide with potent vasorelaxing and natriuretic properties originally isolated from human pheochromocytoma. Adrenomedullin has been reported to be present in normal adrenal medulla, heart, lung and kidney as well as in plasma and urine. ADM shares some structural homology with calcitonin gene related peptide (CGRP). ADM acts on target cells through its unique receptors and CGRP1 receptors. In both cases cyclic AMP seems to be the main second messenger. ADM may function as a circulating hormone and as an autocrine/paracrine mediator involved in the regulation of cardiovascular system and renal function. Plasma concentration of ADM is elevated in patients with congestive heart failure, arterial hypertension, pulmonary hypertension, renal failure and sepsis suggesting its role in pathophysiology of these disorders. Recently another product od adrenomedullin gene, proadrenomedullin N-terminal 20-peptide (PAMP) has been described. This peptide has also vasodilating activity resulting from its inhibitory action on norepinephrine release from sympathetic endings and adrenal medulla.
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PMID:[Adrenomedullin]. 1035 50

Adrenomedullin was originally discovered in human pheochromocytoma but is now known to be widely distributed in various organs. Adrenomedullin is a potent vasodilatator peptide that exerts major effects on cardiovascular function. Plasma adrenomedullin concentration is increased in patients with cardiovascular disease such as hypertension, congestive heart failure, myocardial infarction, renal failure and other diseases. The present review summarizes the recent advances on adrenomedullin research and demonstrates that adrenomedullin is one of the important vasoactive peptides involved in the physiology and pathophysiology of cardiovascular system.
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PMID:[Adrenomedullin. A new peptide involved in the regulation of the cardiovascular system]. 1042 23

Adrenomedullin is a novel vasodilatory peptide originally isolated from pheochromocytoma. Recently, we found that adrenomedullin acts as an autocrine/paracrine apoptosis survival factor for rat endothelial cells. In the present study, we show that adrenomedullin induces the expression of Max, a heterodimeric partner of c-Myc, which may contribute to its ability to rescue endothelial cells from apoptosis. Max is a basic-helix-loop-helix-leucine zipper protein that forms heterodimers with its alternative partners, Mad and Mxi-1, to behave as an antagonist for Myc-Max heterodimer through competition for common DNA targets. The expression of Max is reported to be constitutive and more stable than c-Myc, and serum induces immediate c-Myc stimulation followed by modest Max up-regulation. In quiescent rat endothelial cells, adrenomedullin stimulated the expression of Max without affecting c-Myc. Quantitation with real-time quantitative PCR detected on the ABI Prism 7700 Sequence Detection System revealed that adrenomedullin and calcitonin gene-related peptide (CGRP), as well as serum, up-regulated Max mRNA levels and that down-regulation of Max mRNA after serum deprivation was prevented by adrenomedullin. Neither adrenomedullin nor CGRP affected c-Myc expression. Transfection of a Max-expressing plasmid into endothelial cells rescued the apoptosis induced by serum deprivation. Neutralization with anti-adrenomedullin antiserum or blockade with a CGRP receptor antagonist, CGRP(8-37), reduced Max mRNA levels in growing endothelial cells and enhanced apoptosis after serum starvation. Introduction of an antisense oligodeoxynucleotide against Max mRNA using transferrin receptor-operated transfer led to inhibition of both adrenomedullin-induced up-regulation of Max transcripts and its cell survival effect, whereas random, sense, or missense oligonucleotides were without effect. The negative regulation of E-box-driven transcription by adrenomedullin was demonstrated by using preproendothelin-1 promoter containing c-Myc-Max binding consensus sequence; the promoter activity of preproendothelin-1 was reduced by cotransfecting Max- and Mad-expressing plasmids as well as addition of adrenomedullin and CGRP. The present results demonstrate that adrenomedullin antagonizes serum deprivation-induced endothelial apoptosis by up-regulation of the max gene in an autocrine/ paracrine manner.
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PMID:Induction of max by adrenomedullin and calcitonin gene-related peptide antagonizes endothelial apoptosis. 1044 8

Proadrenomedullin N-terminal 20 peptide (PAMP) is a novel hypotensive peptide found in the N-terminal portion of the precursor of adrenomedullin (AM). Although PAMP and AM originate from the same precursor and exert both a potent hypotensive action, they seem to control blood pressure through different mechanisms. To gain new insight into the anticholinergic actions of PAMP, we determined the effects of PAMP on the tyrosine hydroxylase (TH)- and dopamine beta-hydroxylase (DBH) mRNA expression in the rat pheochromocytoma cell line PC12 stimulated by nicotine. PAMP (> or =1 microM) significantly inhibited the nicotine-induced increases of TH- and DBH mRNA expression in a concentration-dependent manner. Also, PAMP at the concentrations (> or =1 microM) significantly inhibited nicotine-induced cyclic adenosine monophosphate (cAMP) production. These results indicate that the anticholinergic hypotensive actions of PAMP can be explained, at least in part, by its inhibition of the expression of mRNAs coding for catecholamine-synthesizing enzymes, and that the inhibitory effect is mediated by the cAMP/protein kinase A pathway.
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PMID:Effects of PAMP on mRNAs coding for catecholamine-synthesizing enzymes in PC12 cells. 1046 43

Adrenomedullin, originally discovered from pheochromocytoma, is a member of the calcitonin gene-related peptide family. The production and secretion of adrenomedullin by cultured human astrocytes were studied by northern blot analysis and radioimmunoassay. Northern blot analysis showed the expression of adrenomedullin mRNA in cultured human astrocytes. Immunoreactive adrenomedullin concentrations in the culture medium were 29.6+/-1.2 fmol/10(5) cells/24 h (mean +/- SEM, n = 4). Treatment with interferon-gamma (100 U/ml), tumor necrosis factor-alpha (1 and 10 ng/ml), or interleukin-1beta (1 and 10 ng/ml) for 24 h caused >20-fold increases in immunoreactive adrenomedullin levels in the culture medium of human astrocytes. On the other hand, northern blot analysis showed only small increases (approximately 40%) in the adrenomedullin mRNA expression of human astrocytes with either 100 U/ml interferon-gamma or 10 ng/ml interleukin-1beta and no noticeable change with tumor necrosis factor-alpha. Reverse phase HPLC of the medium extracts of human astrocytes treated with interferon-gamma, tumor necrosis factor-alpha, or interleukin-1beta showed that most of immunoreactive adrenomedullin was eluted in the position of adrenomedullin-(1-52). On the other hand, immunoreactive adrenomedullin in the medium of human astrocytes without cytokine treatment was eluted earlier than the adrenomedullin standard, suggesting that this immunoreactive adrenomedullin represents adrenomedullin with some modifications or fragments of the adrenomedullin precursor. The present study has shown the production and secretion of adrenomedullin by human astrocytes and increased secretion of adrenomedullin by cytokines.
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PMID:Increased secretion of adrenomedullin from cultured human astrocytes by cytokines. 1061 10

Adrenomedullin is a peptide of marked vasodilator activity first isolated from human pheochromocytoma and subsequently demonstrated in other mammalian tissues. Using a polyclonal antiserum against human adrenomedullin-(22-52) amide and the avidin-biotin peroxidase complex technique, we have demonstrated by light and electron microscopy that adrenomedullin-like immunoreactivity is widely distributed in the rat central nervous system. Western blotting of extracts of different brain regions demonstrated the fully processed peptide as the major form in the cerebellum, whereas a 14-kDa molecular species and a small amount of the 18-kDa propeptide were present in other brain regions. Immunoreactive neurons and processes were found in multipolar neurons and pyramidal cells of layers IV-VI of the cerebral cortex and their apical processes, as well as in a large number of telencephalic, diencephalic, mesencephalic, pontine and medullary nuclei. Cerebellar Purkinje cells and mossy terminal nerve fibers as well as neurons of the cerebellar nuclei were immunostained, as were neurons in area 9 of the anterior horn of the spinal cord. Immunoreactivity was also found in some vascular endothelial cells and surrounding processes that probably originated from perivascular glial cells. Electron microscopy confirmed the light microscopy findings and showed the reaction product in relation to neurofilaments and the external membrane of small mitochondria. Immunoreactive terminal boutons were occasionally seen. The distribution of adrenomedullin-like immunoreactivity in the central nervous system suggests that it has a significant role in neuronal function as well as in the regulation of regional blood flow.
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PMID:Distribution of adrenomedullin-like immunoreactivity in the rat central nervous system by light and electron microscopy. 1064 Jun 22

Adrenomedullin is a peptide recently isolated from pheochromocytoma that has vasorelaxant and long-lasting hypotensive activities. Plasma levels of adrenomedullin are elevated in patients with congestive heart failure, but the effects of adrenomedullin on the cardiac function are unclear. We, thus, investigated the effects of adrenomedullin on the contraction of rat papillary muscles. We measured the isometric tension and cAMP contents of isolated rat papillary muscles. Adrenomedullin exhibited concentration-dependent inotropic effects. Adrenomedullin also significantly increased intracellular contents of cAMP. Addition of the calcitonin gene-related peptide (CGRP) receptor antagonist inhibited both contractile force and cAMP generation of papillary muscles stimulated by adrenomedullin. The adrenomedullin-induced inotropic effect was further increased in the presence of the phosphodiesterase inhibitor, 3-isobutyl-1-methyl-xanthine (IBMX), while the effect was significantly suppressed by KT5720 and Rp-8-bromoadenosine-3',5'-cyclic monophosphorothioate (Rp-8-Br-cAMPS), protein kinase A inhibitors. These results indicate that adrenomedullin has positive inotropic effects on the heart, at least partially through a cAMP-dependent pathway.
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PMID:Positive inotropic effects of adrenomedullin on rat papillary muscle. 1070 20

Adrenomedullin is a potent vasodilator peptide that was originally identified from human pheochromocytoma. In this study, we investigated the induction of adrenomedullin gene expression in THP-1 acute monocytic leukemia cells during differentiation into macrophage-like cells by 12-O-tetradecanoylphorbol-13-acetate (TPA), and identified a cis-regulatory region of the human adrenomedullin gene responsible for TPA-induced adrenomedullin expression. Upon treatment with TPA (100 ng x mL(-1)) for 24 h, immunoreactive adrenomedullin concentrations in the culture medium and adrenomedullin mRNA levels were increased more than 10-fold, concomitant with the differentiation of THP-1 cells into macrophage-like cells. Actinomycin D abolished the TPA-induced adrenomedullin expression, indicating that the induction of ADM gene expression by TPA was regulated at the transcriptional level. Transient transfection assay revealed that a cis-acting region (positions -70 to -30) of human adrenomedullin gene was necessary for TPA-induced reporter gene expression. This region contains multiple copies of activator protein 2 (AP-2) binding sites, which are bound by purified AP-2 protein, as judged by electrophoretic mobility shift assay. The binding activity to this region was undetectable in nuclear extracts prepared from untreated THP-1 cells, but was increased in extracts prepared from TPA-treated cells. The protein binding was abolished by unlabeled oligonucleotides containing the AP-2 consensus sequence. These results indicate that the region (-70 to -30) of the human ADM gene containing multiple AP-2 binding sites is responsible for TPA-induced adrenomedullin expression in THP-1 cells.
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PMID:Transcriptional control of adrenomedullin induction by phorbol ester in human monocytic leukemia cells. 1084 72

Adrenomedullin is a potent vasodilator peptide originally isolated from pheochromocytoma. Adrenomedullin is produced by various types of cells including neurons and astrocytes. To explore possible pathophysiological roles of adrenomedullin in hypoxic brain, we studied the effects of hypoxia on the expression of adrenomedullin in T98G human glioblastoma cells by radioimmunoassay and northern blot analysis. Expression levels of adrenomedullin mRNA and immunoreactive adrenomedullin levels in the culture medium were increased by hypoxia about six- and about threefold, respectively. Treatment with cobalt chloride increased expression levels of adrenomedullin mRNA about threefold and immunoreactive adrenomedullin levels in the culture medium about threefold in T98G cells. Using actinomycin D, we showed that hypoxia did not cause the stabilization of the adrenomedullin mRNA, suggesting that the increased adrenomedullin mRNA levels in response to hypoxia are caused mainly by increased transcription. Treatment with cycloheximide caused increases in adrenomedullin mRNA levels in both normoxic and hypoxic states, raising the possibility that some protein(s) may act as a suppressor of adrenomedullin gene expression in T98G cells. These findings indicate that adrenomedullin is highly induced during hypoxia in T98G glioblastoma cells and suggest that increased expression of adrenomedullin during hypoxia may be important in the defense against hypoxia or ischemia in the brain.
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PMID:Induction of adrenomedullin during hypoxia in cultured human glioblastoma cells. 1103 71


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