Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Adenosine is produced by renal tissue and has potent effects on renal blood flow and its distribution, glomerular filtration rate (GFR), and the secretion of renin. Intrarenal infusion of adenosine decreases GFR primarily by decreasing glomerular hydrostatic pressure through its effects in increasing afferent arteriolar resistance and possibly decreasing efferent arteriolar resistance. The fall in GFR due to adenosine is accompanied by little change or an increase in total organ blood flow. Regional renal blood flow during adenosine infusion is redistributed, with a greater percentage of total flow going to the juxtamedullary cortex. Intrarenal adenosine produces marked decreases in water and sodium excretion that are proportionally greater than its effect on GFR, suggesting a possible direct tubular action. Intrarenal adenosine also produces a rapid and pronounced inhibition of renin release that appears to be independent of its hemodynamic or tubular effects. A metabolic hypothesis for the control of glomerular filtration rate and renin release with adenosine acting as a mediator is considered, and criteria for establishing an intrarenal role for adenosine in the regulation of renal function are discussed.
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PMID:A proposed role for adenosine in the regulation of renal hemodynamics and renin release. 704 44

Adenosine is a major inhibitory neuromodulator in the central nervous system. One of the receptors mediating the central effects of adenosine is the adenosine A1 receptor. We performed a systematic mutation scan of the coding region of the adenosine A1 receptor gene to explore its variability in the general population. Investigating 40 unrelated healthy subjects by single-strand conformation analysis no sequence changes of likely functional relevance were observed. We detected, however, a frequent T to G substitution at nucleotide position 716 which constitutes the first variant described in an adenosine receptor gene. It was used for fine scale linkage mapping of the A1 gene. Employing a polymerase-chain-reaction-based restriction assay, we genotyped 7 CEPH families (Centre d'Etude du Polymorphisme Humaine) and mapped the receptor in a gene cluster around the renin gene on chromosome 1q31-32.1. In addition, we utilized the 716T/G polymorphism to demonstrate biallelic expression of the adenosine A1 receptor gene in adult human brain.
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PMID:Human adenosine A1 receptor gene: systematic screening for DNA sequence variation and linkage mapping on chromosome 1q31-32.1 using a silent polymorphism in the coding region. 767 73

The purpose of this study was to determine the interactions of the renin-angiotensin system with adenosine and glutamate in the area postrema (AP) of rats. Male Sprague-Dawley rats were anesthetized with urethane. Adenosine, angiotensins (Ang) II, III and their antagonist 1,3-Dipropyl-8-p-sulfophenylxanthine (DPSPX), [Sar1Ile7]Ang III and glutamate antagonist, L-glutamic acid diethyl ester (GDEE) were microinjected into the AP of rats. Our results demonstrated that microinjection of DPSPX significantly attenuated the depressor and bradycardic effects of Ang II and III at low (9.6 pmol) and high dose (480 pmol) of Ang II in normotensive rats. To test the interaction of glutamate and renin-angiotensin system, we found that glutamate antagonist, GDEE, markedly lowered depressor and bradycardic responses of Ang II but did not influence Ang III in rats. On the other hand, microinjection of the Ang antagonist [Sar1Ile7]Ang III 10 min prior to the injection of adenosine significantly altered the cardiovascular effects of adenosine in the AP. In conclusion, the endogenous adenosine and glutamate may influence the renin-angiotensin system on cardiovascular responses in the AP of rats.
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PMID:Adenosine and glutamate modulate the cardiovascular responses of angiotensins II and III in the area postrema of rats. 772 12

Considerable attention has been focused on the purine nucleoside, adenosine, in the control of renal blood flow, epithelial transport, and renin secretion; however, surprisingly little attention has been directed toward the renal effects of purine nucleotides such as adenosine triphosphate (ATP). Recent studies utilizing in vivo micropuncture and in vitro techniques have demonstrated that renal vascular, epithelial, and mesangial cells respond to extracellular ATP via mechanisms distinct from those elicited by adenosine. ATP vasoconstricts afferent but not efferent arterioles whereas adenosine vasoconstricts both vascular segments. Adenosine-mediated afferent arteriolar vasoconstriction is abolished by adenosine receptor antagonists, whereas the response to ATP is enhanced. ATP-mediated vasoconstriction reaches a maximum within seconds of exposure while the vasoconstriction induced by adenosine develops more slowly. L-type calcium channel antagonists such as diltiazem or felodipine prevent the sustained afferent vasoconstriction produced by ATP. Data from micropuncture experiments indicate that peritubular capillary infusion of ATP reduces glomerular pressure and results in marked attenuation of the tubuloglomerular feedback mechanism, which transmits signals from the macula densa to the afferent arteriole. These data support the existence of ATP-sensitive P2 purinoceptors in the preglomerular microvasculature that contribute to the control of renal vascular function via activation of calcium channels.
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PMID:Extracellular ATP in the regulation of renal microvascular function. 814 38

Adenosine (Ado) is a potent vasodilator that has occasionally been shown to cause vasoconstriction. Constrictor responses are generally attributed to A1-receptor stimulation or interactions with the renin-angiotensin system. We describe a previously unreported vasoconstrictor action of Ado and inosine (Ino) in hamster cheek pouch arterioles and examine the mechanism by which these nucleosides induce constriction. Arterioles were dissected from male Golden hamster cheek pouches, transferred to a 37 degrees C tissue chamber, and cannulated at both ends. Changes of luminal diameter in response to Ado were measured to generate cumulative concentration-response curves. The concentration-response curves were biphasic: 10(-6) M Ado elicited an intense, transient constriction, and higher concentrations induced dilator responses. Pretreatment with 8(p-sulfophenyl)theophylline, an Ado receptor antagonist, inhibited the dilator responses but did not alter the constriction. Inhibition of Ado uptake with S-(4-nitrobenzyl)-6-thio-inosine eliminated the constrictor response without altering dilator responses. Similar effects were found after pretreatment with an Ado deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl)adenine hydrochloride. Finally, Ino, a metabolite of Ado, induced constrictions of similar magnitude to those seen with Ado, but at higher concentrations. The constrictor response was focal in nature, suggesting discrete sites of action of Ado. Methylene blue staining after Ado application revealed degranulated mast cells closely associated with the vessel wall, indicating a possible role for mast cell degranulation in the constrictor response. Supporting this idea were the observations that inhibition of degranulation by 10 microM cromolyn blocked the constrictor response, and compound 48/80 (a mast cell secretagogue) caused constriction similar to that elicited by Ado.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nucleoside-induced arteriolar constriction: a mast cell-dependent response. 820 2

Adenosine has profound effects on renal function in experimental animals, but little is known about its role in human subjects. The recent advent of specific adenosine agonists and antagonists suitable for human use, however, now makes it possible to evaluate the influence of this potent vasoactive compound in both normal and pathological states. In this study we assessed the effects of FK-453, a nonxanthine, selective adenosine A1-receptor antagonist, on normal renal hemodynamics, tubular function, and plasma renin release. Eight healthy, male subjects each received three single oral doses of FK-453 (50, 100, and 200 mg) in ascending dose order with random allocation of one matched placebo dose, each on a separate study day. Renal hemodynamics, tubular function, and plasma renin concentrations (PRC) were assessed at baseline and postdose on each study day. Glomerular filtration rate (clearance of 51Cr-labeled EDTA) rose by 18.0%, 3 h after the administration of 100 mg of FK-453 and by 18.3% and 23.5%, 2 and 3 h, respectively, after the 200-mg dose, which was significantly different from the changes following placebo. There were no significant changes in mean arterial blood pressure or effective renal plasma flow (clearance of 125I-Hippuran). In contrast there were statistically significant increases in urine flow rate and osmolar clearance, as well as absolute and fractional excretions of sodium, phosphate, bicarbonate, chloride, magnesium, and uric acid in response to FK-453. No glycosuria or aminoaciduria was detected on urinalysis. There was, in addition, a marked increase in PRC in response to FK-453.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A potential role for endogenous adenosine in control of human glomerular and tubular function. 823 79

Hypernatremia is caused by a water deficit. Cases with hypernatremia and dehydration appear to cluster among children and the elderly with alterations in the level of consciousness thus with no independent access to water. In general, central nervous symptoms prevail. However, thorough examination reveals impaired renal function in many such cases. Animal experiments have shown that rapid increases of the sodium concentration in the renal artery will cause a reduction of renal blood flow (RBF), glomerular filtration rate (GFR) and inhibition of renin secretion, particularly during states of sodium chloride or volume depletion (i.e. with high plasma renin activity). In any other organ hypernatremia leads to vasodilation. The kidney, however, responds with vasoconstriction which can be reversed by the adenosine antagonist theophylline. This finding led to the hypothesis that adenosine mediates the renal response to hypernatremia. Adenosine is generated by the tubules at a higher rate when the kidney is forced to reabsorb large amounts of sodium. In this concept adenosine links metabolic processes of sodium reabsorption with the regulation of organ blood flow causing vasoconstriction via adenosine receptors on the vasa afferentia. This mechanism can explain impaired renal function during acute hypernatremia. It is concluded from experimental evidence that-apart from other therapeutic measures-the recovery of impaired renal function can be improved by administration of the adenosine antagonist theophylline.
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PMID:[Hypernatremia and kidney function]. 832 36

Adenosine is a potent endogenous renal vasoconstrictor. To investigate the sensitivity of the renal circulation to adenosine in cirrhosis, we evaluated kidney function and vasoactive hormones in 20 patients with cirrhosis before and after administration of dipyridamole (0.4 mg/kg, intravenously), a drug that increases extracellular levels of adenosine. In patients with ascites and increased plasma renin activity (6.9 +/- 4.0 ng/ml.hr [mean +/- S.D.]) (n = 7), dipyridamole induced marked reductions in renal plasma flow (from 623 +/- 294 to 374 +/- 188 ml/min, p = 0.03), glomerular filtration rate (from 89 +/- 22 to 48 +/- 16 ml/min, p = 0.009), urine volume (from 7.1 +/- 2.1 to 1.5 +/- 1.1 ml/min, p = 0.0001), free water clearance (from 4.0 +/- 1.7 to 0.4 +/- 0.6 ml/min, p = 0.001) and sodium excretion (from 28 +/- 36 to 7 +/- 15 mu Eq/min, p = 0.05) in the absence of changes in arterial pressure, plasma renin activity and levels of aldosterone, norepinephrine and antidiuretic hormone. In patients without ascites (n = 5) and in patients with ascites and normal plasma renin activity (0.9 +/- 0.5 ng/ml.hr) (n = 8), renal plasma flow and glomerular filtration rate did not change significantly after dipyridamole administration, whereas excretion of sodium and free water was reduced. These results indicate that in cirrhotic patients with ascites and overactivity of the renin-angiotensin system, dipyridamole induces renal vasoconstriction in the absence of changes in systemic hemodynamics, suggesting that these patients are particularly sensitive to the renal vasoconstrictor effect of endogenous adenosine.
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PMID:Effect of dipyridamole on kidney function in cirrhosis. 842 42

Adenosine exerts various effects via membrane receptors in the kidney. It reduces the glomerular filtration rate by altering the resistance of the glomerular arterioles, and it inhibits the release of renin as well as neurotransmission. Adenosine receptors have been further found at different levels of the nephron as well as in glomerular cells. Little is known concerning the mechanisms that regulate the extracellular concentration of adenosine, namely, its production, transport, and catabolism. In the present review we first summarize the pathways of adenosine formation. Then we focus on the ecto-5'-nucleotidase, which seems to represent the major source of extracellular adenosine in the kidney; that enzyme is present in tubular luminal membranes, in fibroblasts, and in mesangial cells. In tubules the enzyme probably plays a role in the salvage of nucleotides present in the primary urine. The activity in fibroblasts is strategically located to convert any AMP released by tubules into adenosine in the close vicinity of glomerular arterioles, and it probably plays a predominant role in most of the regulatory mechanisms involving adenosine. Ecto-5'-nucleotidase activity in fibroblasts increases in anemia, maybe as a response to local hypoxia.
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PMID:Distribution and regulation of renal ecto-5'-nucleotidase: implications for physiological functions of adenosine. 845 51

This review summarizes in the first part the action of adenosine on the kidney. In the second part we discuss the pathophysiological consequences and the possibilities of a pharmacological intervention to improve impaired kidney function. Adenosine causes vasoconstriction in the kidney and reduces glomerular filtration rate (GFR). This action is enhanced in proportion to elevated plasma renin activity. Chronic elevation of ureteral pressure enhances and reduction of renal perfusion pressure attenuates adenosine-induced vasoconstriction. From the kidney-specific relationship between renal blood flow and tubular electrolyte transport the concept is developed which ascribes adenosine a role of a mediator that is essentially contributing to the homeostatic regulation of kidney function. The accumulation of adenosine in the kidney tissue after ischemia or after administration of nephrotoxic substances led to the hypothesis that adenosine is an important intrarenal factor in the pathogenesis of acute renal failure. The possibility to antagonize adenosine actions in the kidney with theophylline was used successfully in a number of experimental studies in acute renal failure and most recently in a study in humans after contrast media administration. Adenosine actions mediated via membrane receptors must be separated from adenosine actions in the cell to increase ATP tissue content. The concept of the "University of Wisconsin" (UW) solution to improve the energy state of the tubular cells appears to be successful, however, we propose that the potential dangerous adenosine actions in the kidney, especially during the reperfusion phase may be antagonized by the administration of theophylline.
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PMID:[Renal effects of adenosine: possible consequences for kidney transplantation]. 846 19


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