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

Adenosine is an important modulator of renal function. Adenosine produced and released within the kidney is thought to participate in the metabolic regulation of glomerular filtration (tubuloglomerular feedback), as well as in regulating renal excretory function and renin secretion. The recent cloning of cDNAs encoding the A1 and A2a adenosine receptors from rat brain allows direct examination of potential sites of adenosine action within the rat kidney. Northern blot analysis of rat kidney poly(A)+ RNA revealed that A1 adenosine receptor mRNA was more abundant in kidney than the A2a adenosine receptor transcript. In situ hybridization with 35S-labeled cRNA probes was used to localize A1 and A2a adenosine receptor mRNAs within the kidney. A1 adenosine receptor mRNA was most abundant in the collecting ducts of the papilla and inner medulla. Collecting ducts in the outermost portion of the inner stripe of the outer medulla and cells of the juxtaglomerular apparatus also expressed A1 adenosine receptor mRNA. A2a adenosine receptor mRNA was localized to the renal papilla. The distribution of A1 and A2a adenosine receptor mRNAs within the rat kidney supports previously postulated roles for adenosine in the regulation of renal hemodynamics, excretory function, and renin secretion.
 ...
PMID:Adenosine receptor gene expression in rat kidney. 148 90

This study was designed to examine: (a) the effects of adenosine and its analogues on renin release in the absence of tubules, glomeruli, and macula densa, and (b) whether adenosine may be involved in a macula densa-mediated renin release mechanism. Rabbit afferent arterioles (Af) alone and afferent arterioles with macula densa attached (Af + MD) were microdissected and incubated for two consecutive 30-min periods. Hourly renin release rate from a single arteriole (or an arteriole with macula densa) was calculated and expressed as ng AI X h-1 X Af-1 (or Af + MD-1)/h (where AI is angiotensin I). Basal renin release rate from Af was 0.69 +/- 0.09 ng AI X h-1 X Af-1/h (means +/- SEM, n = 16) and remained stable for 60 min. Basal renin release rate from Af + MD was 0.20 +/- 0.04 ng AI X h-1 X Af + MD-1/h (n = 6), which was significantly lower (P less than 0.0025) than that from Af. When adenosine (0.1 microM) was added to Af, renin release decreased from 0.72 +/- 0.16 to 0.24 +/- 0.04 ng AI X h-1 X Af-1/h (P less than 0.025; n = 9). However, when adenosine was added to Af + MD, no significant change in renin release was observed. N6-cyclohexyl adenosine (an A1 adenosine receptor agonist) at 0.1 microM decreased renin release from Af from 0.69 +/- 0.14 to 0.39 +/- 0.12 ng AI X h-1 X Af-1/h (n = 5, P less than 0.05). However, 5'-N-ethylcarboxamide adenosine (an A2 adenosine receptor agonist) either at 0.1 microM or at 10 microM had no effect. Theophylline, at a concentration (10 microM) that does not block phosphodiesterase but does block adenosine receptors, increased renin release from Af + MD from 0.21 +/- 0.03 to 0.46 +/- 0.08 ng AI X h-1 X Af + MD-1/h (P less than 0.05; n = 8). The results are consistent with the hypotheses that adenosine decreases renin release via the activation of A1 adenosine receptors, and that adenosine may be an inhibitory signal from the macula densa to juxtaglomerular cells.
 ...
PMID:Possible role of adenosine in the macula densa mechanism of renin release in rabbits. 299 77

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.
 ...
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

We examined the renal effects of a specific adenosine A1-receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 10 micrograms.kg-1.min-1 iv). Since adenosine is a potent inhibitor of renin release, additional experiments were performed with an angiotensin AT1-receptor antagonist (losartan, 10 mg/kg i.v.). DP CPX alone induced a significant (P < 0.05) decrease in afferent arteriolar resistance (RA, 1.83 +/- 0.18 to 1.43 +/- 0.06 dyn.s.cm-5 x 10(10); P < 0.05). This led to a rise in the transcapillary hydraulic pressure difference (delta P, 35 +/- 1 to 43 +/- 2 mmHg; P < 0.05). Surprisingly, the glomerular capillary ultrafiltration coefficient (Kf) fell (0.101 +/- 0.017 to 0.064 +/- 0.009 nl.s-1.mmHg-1, P < 0.05). Additionally, DPCPX infusion resulted in dramatic increases in both urine flow and sodium excretion. With losartan pretreatment, DPCPX did not cause significant changes in RA and delta P. Also, DPCPX increased Kf (0.057 +/- 0.005 to 0.075 +/- 0.008 nl.s-1.mmHg-1, P < 0.05). Furthermore, the large DPCPX-induced increases in urine flow and sodium excretion were largely suppressed by pretreatment with losartan. These data indicate that endogenous adenosine plays a significant role in maintaining afferent arteriolar tone and that the renin-angiotensin system may mediate some of the wide ranging renal effects of adenosine.
 ...
PMID:Effects of selective A1 receptor blockade on glomerular hemodynamics: involvement of renin-angiotensin system. 797 81

The effects of adenosine on glomerular filtration rate and renal blood flow are well documented, but its effects on water and sodium excretion are less well established. Previous studies in the rat have shown that i.v. and intra-aortic administration of adenosine decrease water and sodium excretion. The validity of these findings was challenged recently when it was found that intrarenal administration of adenosine in the rat induced marked diuresis and natriuresis. The aim of the current study was to investigate further the effects of intrarenal administration of adenosine on renal excretory function in the rat. Intrarenal infusion of 2 to 15 micrograms/min of adenosine, although having no effect on systemic arterial pressure, induced a 4-fold increase in water and sodium excretion. Intravenous infusion of adenosine at equivalent doses in the same species and under similar experimental conditions resulted in a 1-fold increase in water excretion, and only a transient increase in sodium excretion, whereas intraaortic adenosine had no effect on either variable. During infusion of adenosine by all three routes, there was a significant decline in glomerular filtration rate, but no change in renal plasma flow. The diuretic and natriuretic effects of adenosine during intrarenal infusion were of a similar order of magnitude in animals maintained for 3 weeks on no sodium, normal sodium or high sodium diet, and did not correlate with plasma renin activity. Simultaneous infusion of 10(-7) M 9-cyclopentyl-1,3-dipropylxanthine, a selective adenosine A1 receptor antagonist, markedly inhibited the diuretic and natriuretic effects of intrarenal adenosine. Intrarenal infusion of N6-cyclohexyladenosine, an adenosine A1 receptor agonist, but not of N' ethylcarboxamidoadenosine, a potent A2 receptor agonist, significantly increased water and sodium excretion. These findings suggest that, in the rat, the diuretic and natriuretic effects of adenosine are 1) fully expressed only during intrarenal administration, 2) absent during intra-aortic administration, 3) not related to prior sodium intake or sodium balance, 4) mediated by the adenosine A1 receptor and 5) dissociated from its effects on glomerular filtration and renal plasma flow.
 ...
PMID:The effects of adenosine on water and sodium excretion. 811 95

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)
 ...
PMID:A potential role for endogenous adenosine in control of human glomerular and tubular function. 823 79

The vasoactive nucleoside adenosine has an important regulatory influence on most aspects of renal function in experimental animals. In this study, we evaluated the effects of intravenous adenosine on systemic and renal hemodynamics, tubular function, and plasma renin concentration in 10 healthy male subjects. Each of the subjects received two intravenous infusions of adenosine (70 micrograms.kg-1.min-1) and saline on three separate study days. There was no significant change in systemic blood pressure in response to adenosine, although there was a significant rise in heart rate postcommencement of adenosine (61.5 +/- 2.9 to 78.0 +/- 7.9 beats/min, 1 h postcommencement of adenosine on day 1, P < 0.01 vs. saline). There was a significant decline in 51Cr-EDTA clearance (glomerular filtration rate) (118.5 +/- 13.2 to 88.0 +/- 8.3 ml/min, P < 0.05 vs. saline) and filtration fraction (19.4 +/- 1.01 to 16.0 +/- 1.03%, P < 0.01 vs. saline) 1 h postcommencement of adenosine, although there was no significant change in 125I-hippuran clearance (effective renal plasma flow). Urine flow rate and osmolar and free water clearance decreased significantly in response to adenosine (particularly on study day 1). There was, in addition, a significant reduction in absolute and fractional excretion rates of sodium, lithium, phosphate, uric acid, chloride, and urea in response to adenosine. There was a rise in plasma renin concentration in response to adenosine, reaching levels of statistical significance on study day 1 (15.0 +/- 2.02 to 22.2 +/- 2.00 microU/ml, 1 h postcommencement of adenosine; P < 0.05 vs. saline). These data are consistent with observations in experimental animals and complement the results of previous studies in man using a selective adenosine A1-receptor antagonist, thereby confirming that adenosine has a significant regulatory influence on human renal function.
 ...
PMID:Effects of intravenous adenosine on renal function in healthy human subjects. 877 Jan 69

Endogenous adenosine has been postulated to have a pathophysiological role both in the initiation and persistence of acute renal failure. The recent advent of selective adenosine receptor antagonists suitable for clinical studies now makes it possible to assess the influence of this vasoactive compound in chronic renal disease. In this study we evaluated the effects of FK453, a non-xanthine selective adenosine A1 receptor antagonist on renal haemodynamics, tubular function and plasma renin release in two groups of patients with stable chronic renal disease. Group I (n = 6) consisted of patients with creatinine clearance > or = 71 ml/min and group II (n = 7) patients with moderate renal impairment (creatinine clearance 31-70 ml/min). Each patient received two single oral doses of FK453 (50 and 200 mg) and one matched placebo dose in a random order, each on separate study days. Renal haemodynamics, tubular function and plasma renin concentrations were assessed at baseline and after the dose on each study day. There were no significant changes in mean arterial blood pressure, effective renal plasma flow (clearance of 125I-hippuran) or glomerular filtration rate (clearance of 51Cr-EDTA) in response to FK453 in either group. In contrast, there were statistically significant increases in urine flow rate and osmolar clearance, as well as absolute and fractional sodium, phosphate, bicarbonate, lithium, uric acid, magnesium and chloride excretion in response to FK453 in both groups of patients. There was, in addition, a significant increase in the plasma renin concentration in response to FK453 in both groups. These data would be consistent with a regulatory role for adenosine in chronic renal disease in the control of tubular function, especially proximal, as well as plasma renin release by activation of the A1 receptor.
 ...
PMID:Functional role of endogenous adenosine in human chronic renal disease. 878 97

We investigated the effects of the adenosine type-1 receptor antagonist FK-838 on salt-induced hypertension in Dahl-Sea salt-sensitive (Dahl S) rats. Dahl S rats fed a high-salt (4% NaCl) diet for 4 weeks were treated with FK-838 or hydrochlorothiazide for 4 weeks and alterations in kidney function and morphologic changes were assessed. FK-838 attenuated the development of hypertension in Dahl S rats, and caused a decrease in aortic weight in a dose dependent fashion. The adenosine antagonist did not produce any detectable metabolic disturbance. The blood pressure reduction by FK-838 was associated with attenuation of glomerular and arterial injury in the kidney. The renal protective effect of FK-838 treatment was associated with a reduction of plasma renin activity and plasma aldosterone concentration. In contrast, the thiazide diuretic, which produced almost the same blood pressure reduction as FK-838, did not attenuate renal damage. These data indicate that adenosine A1 receptor antagonism reduces salt-induced hypertension and the consequent renal injuries.
 ...
PMID:A new adenosine subtype-1 receptor antagonist, FK-838, attenuates salt-induced hypertension in Dahl salt-sensitive rats. 899 53

The purpose of the present investigation was to examine the effects of KW-3902 [8-(noradamantan-3-yl)-1,3-dipropyl-xanthine], a selective and potent adenosine A1 receptor antagonist, in order to clarify the role of adenosine in the control of renal hemodynamics and urine formation in anesthetized dogs. KW-3902 was directly infused into the renal artery to eliminate the systemic effects of the drug. KW-3902 (10 micrograms/kg/min) almost completely inhibited the renal vasoconstriction induced by adenosine via A1 receptors. Intrarenal infusion of KW-3902 did not affect mean arterial pressure, renal blood flow, creatinine clearance, or arterial plasma renin activity, but drastically increased urine flow, urinary excretion of sodium, and osmolar clearance. Inhibition of the renin-angiotensin system using CV-11974 [2-ethoxy-1-((2'-(1-H-tetrazole-5-yl)biphenyl-4-yl) methyl)-1-H-benzimidazole-7-carboxylic acid], a selective AT1 antagonist, did not affect the diuretic action of KW-3902. These data suggest that endogenous adenosine does not play a significant role in the control of renal hemodynamics in whole kidney, but that it plays an important role in preserving body fluid via the A1 receptor independent of the renin-angiotensin system in anesthetized dogs.
 ...
PMID:Effects of KW-3902, a selective and potent adenosine A1 receptor antagonist, on renal hemodynamics and urine formation in anesthetized dogs. 939 79


1 2 Next >>