Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.27.1 (RNase)
 16,360 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is accumulating evidence that adrenomedullin (ADM) is involved in the control of salt and water homeostasis. ADM is considered to act primarily in a paracrine fashion, and since the kidneys are target organs for ADM, we investigated the localization and regulation of ADM and ADM receptor (ADM-R) mRNAs in the kidney. mRNAs for ADM and ADM-R were colocalized in renal vessels, glomeruli, and inner medullary collecting ducts. ADM mRNA was also detected in proximal tubules, whereas ADM-R mRNA was found in distal convoluted tubules. By ribonuclease protection assay, the abundance of ADM mRNA was fourfold higher in cortex than in outer medulla and papilla. In isolated glomeruli, ADM mRNA was threefold higher compared with cortex. Conversely, ADM-R mRNA was fourfold higher in papilla than in renal cortex. This distribution of mRNAs for ADM and ADM-R suggests a cortical source of ADM and a preferential action of ADM in the papilla. Ten days of feeding a low-salt (0.02%) or a high-salt diet (4%) did not change ADM mRNA or ADM-R mRNA in any kidney zone.
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PMID:Effects of dietary salt on adrenomedullin and its receptor mRNAs in rat kidney. 968 4

Recent studies have suggested that adrenomedullin (AM) may play a role in the pathophysiology of heart disease, though the specific cardiac receptors involved have not been defined. RT-PCR cloned fragments of three putative AM/calcitonin gene-related peptide (CGRP) receptors were used to established a quantitative RNase protection assay to identify and quantitate expression of receptor mRNAs in heart and in cardiac myocytes. Intact rat heart expressed mRNA encoding the putative AM/CGRP receptors RDC1 and CRLR at 37- and 15-fold higher levels, respectively, than the AM-selective receptor L1, with a qualitatively similar profile in cultured neonatal cardiac myocytes. The high level of expression of RDC1 and CRLR suggests that both AM and CGRP may have direct actions on the cardiac myocyte via common receptors that can interact with either ligand.
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PMID:Cardiac expression of genes encoding putative adrenomedullin/calcitonin gene-related peptide receptors. 978 7

Our study aimed to investigate the influence of tissue hypo-oxygenation on the adrenomedullin (ADM) system in vivo. For this purpose, male Sprague-Dawley rats were exposed to normobaric hypoxia (8% oxygen) or to functional anemia [0.1% carbon monoxide (CO)] or to cobalt chloride (60 mg/kg) for 6 h. Messenger RNA levels for ADM and its receptor (ADM-R) were assessed in diverse organs by RNase protection assay. Additionally, ADM protein concentrations in these organs, as in plasma, were determined by a RIA. We found that ADM mRNA abundance increased in response to hypoxia and to CO inhalation up to 15-fold in all organs examined. Similarly, ADM-R mRNA abundance increased during hypoxia and CO inhalation in all organs examined with exception of the liver. The effects of hypoxia and of CO inhalation on ADM and ADM-R mRNAs were mimicked by injection of cobaltous chloride. Hypoxia also significantly increased ADM protein content in all organs, and plasma levels of ADM rose twofold in response to hypoxia and CO inhalation. These findings indicate that tissue hypoxia leads to a widespread activation of the ADM system, which comprises a parallel stimulation of ADM and ADM receptor mRNA as enhanced ADM protein synthesis and secretion. The ADM system may, therefore, play a significant role in the physiological response to tissue hypoxia. It appears that ADM and ADM-R belong to the family of classic oxygen-regulated genes, which are activated by a decrease of the pericellular oxygen tension through the same intracellular signaling cascade.
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PMID:Tissue hypoxygenation activates the adrenomedullin system in vivo. 1066 55

Natriuretic peptides (NPs), such as atrial natriuretic peptide (ANP), C-type natriuretic peptide (CNP), and adrenomedullin (ADM), are endogenous vasodilators acting via specific receptors. This study addressed the question of how pulmonary artery (PA) responses to these peptides and the gene expression of their receptors are modulated in pulmonary hypertension rat models exposed to chronic hypoxia. In this study, isometric tension was measured in PA rings exposed to these NPs and 8-bromoguanosine 3', 5'-cyclic monophosphate (8-bromo-cGMP). It was compared with messenger ribonucleic acid (mRNA) levels of NP-A and -B receptors, which bind to ANP and CNP, respectively, as determined by ribonuclease (RNase) protection assay. Chronic hypoxia increased the maximal relaxation elicited by ANP, but the responses to CNP and 8-bromo-cGMP were unchanged. Chronic hypoxia did not change NP-A and -B receptor mRNA levels. The results showed that pulmonary artery response to atrial natriuretic peptide is selectively enhanced, possibly via a post-transcriptional modulation of its receptor in chronically hypoxia rats. These pharmacological characteristics of atrial natriuretic peptide are consistent with the hypothesis that the atrial natriuretic peptide system is protective against the progression of pulmonary hypertension.
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PMID:Modulated vasodilator responses to natriuretic peptides in rats exposed to chronic hypoxia. 1070 11

The aim of our study was to clarify whether atrial (ANP) and brain (BNP) natriuretic peptides and the hypotensive peptide adrenomedullin (ADM) are regulated differently in the rat heart in the two-kidney, one-clip model of renovascular hypertension. We assessed messenger ribonucleic acid (mRNA) abundance and distribution of ANP, BNP and ADM in the ventricles and atria of rats after unilateral renal artery stenosis (clipping). Rats were clipped for 6 h or 1, 2 or 4 days and mRNA levels were assessed semiquantitatively in left and right atria and ventricles by RNase protection assay. Left ventricular BNP mRNA up-regulation (4.3-fold after 6 hours) preceded ANP up-regulation (4.5-fold after 1 day) and seemed to be transient, whereas ANP mRNA levels were still elevated at day 4 (2.4-fold vs. sham). The right ventricle and the atria did not participate in these responses. Despite the massive changes of natriuretic peptide mRNAs, ADM mRNA did not change in either the ventricles or the atria. In contrast to ANP and BNP mRNA, which predominate in atrial tissue, mRNA for adrenomedullin is equally distributed in ventricles and atria. Plasma levels of immunoreactive (ir)-ANP and ir-BNP changed in parallel with left ventricular mRNA levels. Our findings suggest that renovascular hypertension induced by clipping the renal artery leads to immediate, but independent, up-regulation of ANP and BNP mRNA in the left ventricle whereas adrenomedullin mRNA is not changed.
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PMID:Different regulation of left ventricular ANP, BNP and adrenomedullin mRNA in the two-kidney, one-clip model of renovascular hypertension. 1141 16

The adrenomedullin (AM) gene codifies for two bioactive peptides, AM and proAM N-terminal 20 peptide (PAMP). We have found two forms of the AM mRNA. Form A is devoid of introns and results in a prohormone containing both peptides. Form B retains the third intron, which introduces a premature stop codon, producing a shorter prohormone with only PAMP. Tissues with a higher B/A ratio were more immunoreactive for PAMP than for AM. The form B message was found in the cytoplasmic compartment, thus excluding that the longer message was a result of contaminating nuclear mRNA. Form B was found in cells that express PAMP but not AM. mRNA expression in a variety of cell lines was investigated by ribonuclease protection assay and form B was found in significant amounts in two of them. Treatments that modify AM expression, such as exposure to hypoxia, were shown to change the B/A ratio and the relative secretion of AM and PAMP, indicating that the splicing mechanism for AM can be modulated and is physiologically relevant. Analysis of the sequence of the third intron and the fourth exon of the AM gene found motifs compatible with a highly regulated alternative splicing mechanism.
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PMID:Alternative splicing of the proadrenomedullin gene results in differential expression of gene products. 1146 74

Levels of expression of adrenomedullin (AM) in the uterus have been reported to vary with the reproductive cycle. This study examines the relationships among uterine AM mRNA, the stage of the estrous cycle, and circulating estradiol and progesterone in cycling rats and in ovariectomized (OVX) rats without or with estrogen replacement (ER). Strong AM mRNA, AM immunoreactivity, and pro-AM NH2-terminal 20 peptide (PAMP) immunoreactivity were observed in endometrial stroma by use of in situ hybridization and immunocytochemistry. Endometrial expression was particularly intense at proestrus and estrus, with weaker expression in the myometrium. By RNase protection assay, significant differences in AM mRNA between the stages of the estrous cycle could not be established. However, levels of AM mRNA were positively correlated with plasma estradiol in cycling rats (r = 0.56, P < 0.005) and in OVX and ER rats (r = 0.92, P < 0.001) and were not correlated with plasma progesterone. Levels of AM mRNA were significantly reduced after OVX compared with cycling rats, and ER restored AM mRNA to levels equivalent to those seen at the peak of the cycle (proestrus). In conclusion, although AM expression in the uterus varies throughout the estrous cycle, it is more closely correlated with circulating estradiol levels than with the stage of the cycle itself.
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PMID:Adrenomedullin expression in rat uterus is correlated with plasma estradiol. 1173 94

To study the effect of septicaemia, the temporal changes in tissue adrenomedullin (AM) and preproAM mRNA levels were studied in the heart and blood vessels after lipopolysaccharide (LPS) injection. Radioimmunoassay and solution hybridization-RNase protection assays were used to follow the changes in AM and its mRNA levels respectively after intraperitoneal injection of 10 mg/kg LPS in rats. The preproAM mRNA levels increased at 1 h in the right atrium after LPS injection, while the AM contents decreased at 1 h in the left atrium. The preproAM mRNA levels increased at 3 and 6 h in the left ventricle, whereas it increased at 6 h in the right ventricles after LPS injection. There was an increase in preproAM mRNA levels at 1 and 3 h in the mesenteric artery, while AM levels were increased at 1, 3 and 6 h. However, there were no such changes in the thoracic aorta. There were also increases in tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta and IL-6 in the heart, and in the mesenteric artery (TNF-alpha and IL-1beta) and in thoracic aorta (IL-1beta and IL-6). The present results suggest that the biosynthesis and secretion of AM may be increased in cardiovascular tissues of rats injected with LPS, and that AM may play multiple roles in inflammation.
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PMID:Adrenomedullin gene expression and levels in the cardiovascular system after treatment with lipopolysaccharide. 1575 40

The aim of the present study was to determine the temporal changes in tissue adrenomedullin (AM) and cytokine contents and cytokine and preproAM mRNA levels in the kidney, liver, adrenal gland and spleen of lipopolysaccharide (LPS)-treated rats. Rats were injected with LPS (10 mg/kg, i.p.). Radioimmunoassay and solution hybridization-RNase protection assays were used to follow the changes in AM and its mRNA levels, respectively; ELISA and reverse transcription-polymerase chain reaction were used to follow the changes in cytokines and their mRNA levels, respectively. In the kidney, the preproAM mRNA levels were increased 1 and 3 h after LPS treatment, whereas AM levels were decreased at 3 h. Interleukin (IL)-6 and IL-1beta levels were increased at 3 and 6 h, respectively. The preproAM mRNA levels were elevated in the liver 3 h after LPS injection. Concentrations of tumour necrosis factor (TNF)-alpha and IL-1beta were increased at l and 6 h, respectively. There were no changes in the levels of either preproAM mRNA or AM in the adrenal gland and the spleen. In the spleen, TNF-alpha levels were elevated at 1 and 3 h after LPS injection and IL-1beta was elevated at 1 and 6 h after LPS injection, whereas in the adrenal gland IL-1beta was elevated at 6 h after injection. The mRNA levels of the three cytokines were elevated at all three time intervals examined in the kidney, liver, adrenal gland and spleen, with the exception that TNF-alpha mRNA was not elevated in the adrenal gland at 6 h after LPS injection and IL-1beta mRNA was not elevated in the spleen at 3 and 6 h. The plasma concentrations of TNF-alpha were increased at 1 and 3 h after LPS injection, whereas plasma concentration of IL-1beta and IL-6 were elevated at 3 and 6 h for both. The present results suggest that the biosynthesis and secretion of AM may be differentially regulated in various tissues of rats injected with LPS and that AM may interact with cytokines during inflammation.
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PMID:Differential induction of adrenomedullin, interleukins and tumour necrosis factor-alpha by lipopolysaccharide in rat tissues in vivo. 1644 78

The aim of the present study was to assess the changes in gene expression and peptide adrenomedullin (AM) levels in cardiovascular and other tissues in the streptozotocin-diabetic rats. For this purpose, diabetes was induced by intraperitoneal injection of streptozotocin (STZ, 65 mg/Kg body weight). Half of the diabetic rats were subcutaneously injected with insulin in the afternoon (4 units/day) one week after STZ injection until the day before killing. Control rats received only saline injection. AM mRNA was determined in cardiovascular and other tissues of streptozotocin-diabetic rats using solution-hybridization-RNase protection assay. Circulating AM and peptide AM in cardiovascular and other tissues were estimated using a specific radioimmunoassay. There were increases in preproAM mRNA levels in the left and right ventricles and in the thoracic aorta in both the 2-week and 4-week diabetic rats, but not in the two atria, the mesenteric artery and the lung. In the 2-week diabetic rats, there were decreases in AM contents in the two atria and the lung but an increase in the thoracic aorta. In the 4-week diabetic rats, there were bigger decreases in the atria and also a decrease in the left ventricle. The plasma AM levels were not changed but there was an increase in the excretion of AM in the urine. Our results suggest a possible increase in AM release in the heart and the thoracic aorta in the 2-week and 4-week diabetic rats.
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PMID:Adrenomedullin gene expression and peptide levels in the heart and blood vessels of streptozotocin-diabetic rats. 1722 6


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