Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiotensin II (ANG II) is the primary mediator of the renin-angiotensin system, which has an important functional role in cardiovascular homeostasis. The angiotensin receptor and its functional correlates have been redefined by the cloning of angiotensin receptors and the discovery and widespread study of specific nonpeptide ANG II-receptor antagonists losartan (AT1 selective) and PD123177 (AT2 selective). With these antagonists, it has been possible to extend the concept of ANG II-receptor heterogeneity to virtually every tissue and species. The losartan-sensitive sites have been shown to mediate all of the major ANG II-induced biologic effects, including vasoconstriction, aldosterone and catecholamine release, and central, ANG II-induced drinking behavior. The function of the AT2 site is not fully understood, but it may be involved in neuronal ion channel modulation and in fibroblast collagen metabolism. The presence of AT2 sites in fetal tissues and in discrete locations in the brain has encouraged continued research. Losartan, which represents the first of a new class of therapeutic agents, is currently undergoing clinical trials. A growing number of other AT1-selective ANG II-receptor antagonists are under development, including L-158,809, SKF 108566, and GR117285. Rat AT1-receptor subtypes have been cloned and sequenced (AT1A and AT1B). Human ANG II receptors have also been cloned and shown to have high affinity for losartan. A number of atypical angiotensin-binding sites have been identified from mycoplasma, amphibians, and mouse neuroblastoma, which are not sensitive to either losartan or PD123177.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Angiotensin II receptors and functional correlates. 129 Jun 17

A simplified and sensitive method for measuring expression levels of type-1 angiotensin II (AT1) receptor subtypes, AT1A and AT1B, was established. The two receptor cDNAs were co-amplified and measured by polymerase chain reaction using primers based on the corresponding receptor subtype genes. Both AT1A and AT1B mRNAs were widely expressed in the rat tissues including adrenal gland, kidney, heart, aorta, lung, liver, testis, pituitary gland, cerebrum and cerebellum. AT1A mRNA was predominantly expressed in the rat tissues examined except adrenal gland and pituitary gland where AT1B mRNA was predominantly expressed. Sodium depletion did not change mRNA levels of AT1A and AT1B in the all tissues. However, both AT1A and AT1B mRNA levels in the heart and aorta were down-regulated by treatment with AT1 specific antagonist, TCV 116. In contrast, AT1B mRNA in the adrenal gland was mainly reduced by the treatment. These results suggest that the expression level of AT1B mRNA in the adrenal gland depends on the activity of the renin-angiotensin-aldosterone system (RAAS) and both receptor subtypes mediate contraction and hypertrophy of the smooth and cardiac muscles via the RAAS.
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PMID:Differential gene expression and regulation of type-1 angiotensin II receptor subtypes in the rat. 138 88

The relation between serum cortisol, plasma renin activity, angiotensin II (Ang II), or aldosterone levels and peripheral blood cell (mononuclear leukocytes and platelets) angiotensin II type 1A (AT1A) and 1B (AT1B) receptor mRNA levels was examined in both patients with Cushing's syndrome (seven patients with Cushing's syndrome due to unilateral adrenal cortical adenoma) and control subjects (seven normotensive patients with renal cell carcinoma). Blood was collected from each participant for estimation of plasma renin activity and plasma angiotensin II, aldosterone, and cortisol concentrations and for isolation of mononuclear leukocytes and platelets, which were then used to measure AT1A and AT1B receptor mRNA levels before and after adrenalectomy with the use of reverse transcription-polymerase chain reaction. In patients with Cushing's syndrome, both mononuclear leukocyte and platelet AT1A mRNA levels, which were elevated, were reduced after removal of the adrenal tumors, whereas AT1B receptor mRNA levels of both types of blood cells did not significantly change after adrenalectomy. In contrast, in control subjects, both AT1A and AT1B receptor mRNA levels did not significantly change after unilateral adrenalectomy and nephrectomy. In the adrenal tumors of patients with Cushing's syndrome, gene expression of AT1A receptor was decreased compared with that from adrenals of control subjects. AT1A receptors of the platelets were shown to be upregulated in a manner similar to those of mononuclear leukocytes in patients with Cushing's syndrome. These results suggest that cortisol excess is an important factor upregulating AT1A receptor mRNA levels in human blood cells.
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PMID:Gene expression of angiotensin II receptor in blood cells of Cushing's syndrome. 749 Jan 36

Activation of the renin-angiotensin system by sodium deficiency is associated with reciprocal changes in the expression of angiotensin II receptors in adrenal glomerulosa and vascular smooth muscle cells. The effects of dietary sodium changes on the expression of brain angiotensin receptor subtype 1 (AT1) mRNAs were examined in rats maintained on normal, low, and high sodium intake for 3 weeks. Plasma aldosterone and renin activity were elevated in rats maintained on a low salt diet compared with normal rats and were reduced in rats maintained on a high salt diet. These results are consistent with previous findings on the effects of altered dietary sodium on the renin-angiotensin system. The expression of AT1A and AT1B receptor subtype mRNAs was determined by quantitative reverse transcriptase-polymerase chain reaction during changes in sodium intake. The results revealed that sodium deprivation enhanced the expression of AT1B receptors in decorticated brains by 164% compared with high sodium intake. Conversely, high sodium diet increased the expression of AT1A receptors by 155% in the brain compared with low sodium intake. These data suggest that AT1A and AT1B receptors play reciprocal roles in central mechanisms for the control of fluid homeostasis. Further analysis of the molecular biology of angiotensin II receptor regulation in the brain may provide new insights into the interplay between the renin-angiotensin system and blood pressure regulation and also into the role of angiotensin II in the pathogenesis of essential hypertension.
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PMID:Regulation of angiotensin II receptors in rat brain during dietary sodium changes. 750 98

Recent studies have revealed that angiotensin II (Ang II) interacts with two pharmacologically different types of seven-transmembrane domain receptors, hence named Ang II type 1 and type 2 (AT1 and AT2) receptors. cDNAs for the AT1 receptor have been cloned, and the existence of two receptor subtypes, AT1A and AT1B, has been revealed in rat and mouse. This study presents a new approach for the specific quantification of AT1A and AT1B receptor mRNAs by reverse transcription and polymerase chain reaction amplification in the presence of an AT1 receptor mutant cRNA as internal standard. Absolute quantities of mRNA are then determined by extrapolation using the standard curve generated with the internal standard. Moreover, addition of this internal standard to each tube controls for both reverse transcription and polymerase chain reaction amplification in each sample. In male Wistar rats, the highest absolute AT1A receptor mRNA levels were found in liver and kidney and those for AT1B receptor mRNA in the pituitary. Expressed as a percentage of total AT1A+AT1B receptor mRNA content, AT1A receptor mRNA content was 100% in liver, 85% in lung, 73% in kidney, 65% in aorta, 48% in adrenals, and 15% in the hypophysis. Since this approach can determine absolute AT1A and AT1B receptor mRNA quantities in different organs, it allows the study of the regulation of their expression under different pathophysiological conditions. After sodium depletion, known to induce hyperactivity of the renin-angiotensin system, adrenal AT1A and AT1B receptor mRNA levels were increased by 60% and 110%, respectively. In contrast, in renovascular hypertension (two-kidney, one clip), also associated with elevated circulating plasma renin activity, adrenal AT1B receptor mRNA levels decreased by 50%, whereas there was no change in those of AT1A. Therefore, the differential distribution and regulation of these two receptor subtypes suggest that each of them might be involved in the mediation of different biological effects of Ang II.
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PMID:Tissular expression and regulation of type 1 angiotensin II receptor subtypes by quantitative reverse transcriptase-polymerase chain reaction analysis. 752 76

The aim of this investigation was to examine the interrelation between renal mRNA levels of renin and angiotensin II receptor type 1 (AT1) in a renin-dependent form of experimental hypertension. Rats were studied 4 weeks after unilateral renal artery clipping. Mean blood pressure and plasma renin activity were significantly higher in the hypertensive rats (n = 10 206 +/- mm Hg and 72.4 +/- 20.9 ng/mL-1/h-1, respectively) than in sham-operated controls (n = 10, 136 +/- 3 mm Hg and 3.3 +/- 0.5 ng/mL-1/h, respectively). Northern blot analysis of polyA+ RNA obtained from the kidneys of renal hypertensive rats showed increased levels of renin mRNA in the clipped kidney, whereas a decrease was observed in the unclipped kidney. Plasma renin activity was directly correlated with renin mRNA expression of the poststenotic kidney (r = .94, P < .01). AT1 mRNA expression was lower in both kidneys of the hypertensive rats. This downregulation was specific for the AT1A subtype since the renal expression of the AT1B subtype remained normal in hypertensive rats. The downregulation of the renal AT1A receptor may be due to high circulating angiotensin II levels. This is supported by the significant inverse correlation (r = .71, P < .01) between plasma renin activity and AT1A mRNA expression measured in the clipped kidney of the hypertensive rats.
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PMID:Renin and angiotensin II receptor gene expression in kidneys of renal hypertensive rats. 759 Oct 11

At least two distinct genes (AT1A and AT1B) encode type 1 angiotensin II (AT1) receptors in rodents. Receptor binding and Northern blot analysis have clearly demonstrated the presence of AT1 receptors and AT1-receptor mRNA in many tissues but fail to differentiate which type 1 receptor subtype is expressed. A reverse-transcriptase polymerase chain reaction restriction fragment length polymorphism (RT-PCR-RFLP) assay was developed to differentiate the expressed mRNA by subtype. Expression of AT1A was clearly evident in kidney, liver, adrenal gland, ovary, brain, testes, adipose tissue, lung, and heart of adult mice. AT1B was absent from most of these tissues but was detectable in brain, testes, and adrenal gland. No significant differences in expression were evident in kidney, liver, brain, lung, or heart from 16.5- or 18.5-gestation-day fetuses, and only AT1A was evident in placenta. Expression of AT1B was confirmed in adrenal gland, brain, and testes, using a primer set that specifically amplifies only AT1B mRNA. Expression of AT1A and AT1B was also examined in As4.1 cells, a renin-expressing mouse kidney tumoral cell line. Receptor binding and competition assays using AT1- and AT2-receptor antagonists revealed that only AT1 receptors are present on the cell surface. Extremely low levels of AT1-receptor mRNA was detected by Northern blot, and RT-PCR-RFLP analysis revealed that only the AT1A subtype is expressed in this cell line. Despite the high homology between the coding sequence of the AT1A and AT1B genes, they exhibit disparate tissue-specific expression profiles.
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PMID:Differential expression of angiotensin receptor 1A and 1B in mouse. 807 5

There are two major isoforms of the angiotensin II receptor, type 1 (AT1) and type 2 (AT2). AT2 is distinguished from AT1 with respect to its ligand selectivity, its insensitivity to non-hydrolyzable GTP analogues, and its as yet unidentified biological functions. In the present study we have expression-cloned AT2 cDNA from a cDNA library of a rat pheochromocytoma cell line (PC12w). Rat AT2 cDNA encodes a 363-amino acid protein that has seven transmembrane domains. AT1 is the closest in homology to AT2 but with only a 32% identity of amino acid sequence. Stably expressed in COS-7 cells, the receptor showed selective binding to AT2-specific ligands PD123319 and CGP42112A but not to the AT1-specific ligand, losartan. Northern blot analysis revealed that the mRNA of rat AT2 was expressed not only in PC12w cells but also in the adrenal glands and in the inferior olive of the brain, both of which are known to contain AT2 type binding sites. The expressed AT2 receptor mediated angiotensin II-induced inhibition of protein tyrosine phosphatase, an action that was dependent on a pertussis toxin-sensitive G-protein-coupled mechanism in COS-7 cells. The AT2-specific ligand CGP42112A was an agonist rather than antagonist in the inhibition of phosphotyrosine phosphatase. AT2 did not cause a decrease in cGMP in PC12w or COS-7 cells expressing AT2 stably. These results indicate that the AT2 receptor is structurally and functionally different from AT1 and suggest novel functional roles of the renin-angiotensin system in cross-talk with phosphotyrosine signaling by modulating protein phosphotyrosine levels.
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PMID:Molecular cloning of a novel angiotensin II receptor isoform involved in phosphotyrosine phosphatase inhibition. 822 11

The localization of the two type 1 angiotensin II receptor subtype (AT1A and AT1B) messenger RNAs in the 19-day-old rat fetus was studied by in situ hybridization. AT1 receptor mRNAs were detected in target organs of the renin-angiotensin system such as the kidney, adrenal gland, liver, heart, large arteries, and pituitary gland. In addition, angiotensin II receptors were present in specialized mesenchymal cells surrounding the cartilage, in the pericardium, in the lung, and in the undifferentiated mesenchymal tissue. The AT1A subtype was predominant in all tissues and organs except the adrenal cortex and glomeruli in the kidney, which expressed both AT1A and AT1B mRNAs. The widespread distribution of AT1 receptors in tissues and organs involved in hydromineral equilibrium and blood pressure regulation shows that during fetal development angiotensin II may already act as a regulator of the cardiovascular system. An effect on cellular differentiation and/or proliferation via AT1 receptors is also suggested by their location in several mesenchymes.
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PMID:Distribution of type 1 angiotensin II receptor subtype messenger RNAs in the rat fetus. 828 25

The renin-angiotensin system has been implicated in the hypertrophic adaptation of the heart to exogenous pathological loads, such as hypertension and aortic stenosis; however, the role of this hormonal system in the cardiac adaptations to physiological loads, such as chronic exercise conditioning, has not been established. We therefore studied the effect of angiotensin receptor 1 (AT1) blockade on the chronic cardiac responses of rats subjected to an 8-wk swimming program. Compared with matched sedentary controls, untreated swimmers increased their left ventricular weights by 13%, and swimmers treated with the AT1 antagonist L-158809 increased their left ventricular weights by 11% (both P < 0.05 vs. sedentary controls). The incorporation of labeled amino acids into the heart at the time of death was unchanged in all groups, and therefore the increase in heart weight in both swim-conditioned groups appeared to reflect a decrease in the rate of protein degradation in the heart. Hearts from both swim-conditioned groups manifested an increase in the V1-predominant myosin isoform pattern but not an increase in atrial natriuretic factor mRNA expression or protein kinase C translocation. The fact that these patterns of adaptation are preserved in exercised conditioned animals treated with an AT1 antagonist suggests that the chronic hypertrophic response of the heart to physiological loads is not influenced by the renin-angiotensin system.
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PMID:Angiotensin receptor 1 blockade does not prevent physiological cardiac hypertrophy in the adult rat. 887 51


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