Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q92565 (GFR)
 4,179 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The action of theophylline on the adenosine-induced decrease in renin release was studied in anesthetized dogs. Adenosine inhibited renin release, decreased GFR and fractional sodium excretion, and decreased the concentration of angiotensin II in the renal lymph. Theophylline (5 mumol/min intrarenally) had no significant effect on GFR or RBF yet produced a significant increase in the release of renin and the fractional excretion of sodium. The intrarenal infusion of adenosine (3 X 10(-7) mol/min) during theophylline infusion produced no effect on GFR or RBF, but fractional sodium excretion and renin release were significantly decreased. Adenosine was infused at a lower dose (3 X 10(-8) mol/min) during theophylline (5 X 10(-6) mol/min) infusion in a second group of dogs. With the exception of fractional sodium excretion, all effects of adenosine were effectively antagonized by theophylline. Theophylline at 5 X 10(-6) mol/min, which stimulates renin release and effectively antagonizes the renal effects of adenosine, had no detectable effect on cAMP measured in renal cortex. Furthermore, no change in cortical cAMP was observed until theophylline was increased 50-fold over the dose effective in antagonizing adenosine. These findings demonstrate that theophylline, at concentrations having no effect on cortical cAMP, antagonizes the effect of adenosine on renin release. The results are also consistent with the view that theophylline stimulates renin release by a mechanism other than its action on cAMP.
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PMID:Antagonistic effect of theophylline on the adenosine-induced decreased in renin release. 608 79

Adenosine infusion is associated with natriuresis as well as antinatriuresis. The physiologic significance of these opposite effects is unknown but may have to do with different conditions of ischemia, in which adenosine accumulates. These effects were characterized in the rat. First, intrarenal and systemic infusions within one animal were performed. Infusing 10 micrograms/min into the left renal artery increased sodium by approximately 50%; however, the subsequent infusion of 50 micrograms/min into the thoracic aorta decreased sodium excretion by approximately 60%, in association with a small reduction of blood pressure. Second, to explore the effect of intrarenal adenosine in tubular sodium handling, free-flow micropuncture experiments were performed. The intrarenal infusion of 10 micrograms/min again caused sodium excretion, but no change in GFR, volume, and sodium deliveries up to the early distal tubule was found. Apparently, the direct effect of adenosine in the kidney is sodium excretion, by a tubular action beyond the early distal tubule. Third, to further characterize the indirect effect, which apparently is sodium retention, adenosine was infused systemically at low rates, in order to avoid a decrease in blood pressure. A 25 micrograms/min infusion again caused sodium retention, in the absence of a fall in blood pressure. After acute left renal denervation, the antinatriuretic effect disappeared in the denervated kidney but remained in the right kidney. These data suggest that increased intrarenal adenosine suppresses sodium reabsorption at some distal nephron site, appropriately decreasing the workload of the kidney. On the other hand, systemic adenosine stimulates sodium reabsorption, an effect that is appropriate to improve systemic circulation and depends on the renal nerves.
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PMID:Adenosine and renal sodium handling: direct natriuresis and renal nerve-mediated antinatriuresis. 858 28

Nephron function is stabilized by tubuloglomerular feedback (TGF). TGF operates within the juxtaglomerular apparatus, sensing changes in tubular flow and eliciting compensatory changes in single nephron GFR (SNGFR). The mediator(s) of TGF remains unconfirmed. One theory is that ATP consumed in active transport by the macula densa leads to formation of adenosine, which causes glomerular vasoconstriction. We performed micropuncture in rats to test this hypothesis. Adenosine activity was manipulated by microperfusing nephrons with adenosine A1 receptor blocker, A1-agonist, or 5'-nucleotidase inhibitor. Effects on TGF were characterized by changes in TGF efficiency (the compensation for small perturbations in tubular flow) and by changes in the maximum range over which TGF can cause SNGFR to change. These data were further applied to generate TGF profiles [SNGFR versus late proximal flow (V(LP))]. TGF efficiency was significantly reduced by blocking A1-receptors. TGF efficiency, TGF range, and the slope of the TGF profile (DeltaSNGFR/DeltaV(LP)) were all significantly reduced by blocking 5'-nucleotidase. When adenosine activity was clamped by combining 5'-nucleotidase inhibitor with A1-agonist to determine whether TGF requires adenosine to be present or to fluctuate, the TGF slope was reduced by 83%, indicating that adenosine activity must fluctuate for normal TGF to occur and that adenosine is a mediator of TGF.
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PMID:Adenosine formed by 5'-nucleotidase mediates tubuloglomerular feedback. 1090 45

Adenosine, one of the endogenous modulators in renal hemodynamics, has recently been shown to be a mediator of tubuloglomerular feedback (TGF). Dilazep augments endogenous adenosine actions by blocking its cellular uptake. Our purpose in the present study was to clarify the effects of dilazep on renal microcirculation and the TGF mechanism. Clearance and micropuncture experiments were performed in anesthetized rats. TGF responsiveness was assessed in superficial nephrons by measuring the changes of early proximal flow rate (EPFR) in response to loop perfusion at 0-40 nl/min with artificial tubular fluid (ATF). Under dilazep administration (0.3 mg/kg+0.3 mg/kg/h i.v.) systemic BP and GFR were decreased and renal plasma flow was unaltered; as a result, the filtration fraction tended to decrease (p=0.076). Renal vascular resistance was reduced, but not to a significant degree. The reduction in EPFR by loop perfusion was similar between controls (47 +/- 2%) and rats administered dilazep i.v. (44 +/- 5%). Intraluminal application of dilazep in ATF suppressed TGF-mediated EPFR reduction to by 46 +/- 4%, 43 +/- 7%, and 37 +/- 3% at dilazep concentrations of 10(-6), 10(-5), and 10(-4) mol/l, respectively. TGF suppression with 10(-4) mol/l dilazep was reversed by co-perfusion of 10(-5) mol/l DMPX, a selective adenosine A2 receptor antagonist. DMPX alone did not affect TGF response. In conclusion, these results indicate that systemic dilazep dilates postglomerular arterioles and does not affect TGF, and thus reduces GFR. A pharmacological concentration of dilazep applied to single nephrons clearly attenuates TGF, indicating afferent arteriolar vasodilatation. Extracellular adenosine augmented by dilazep dilates glomerular vessels at both afferent and efferent sites, probably via the activation of A2 receptors.
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PMID:Effects of a nucleoside transporter inhibitor, dilazep, on renal microcirculation in rats. 1235 50

Adenosine coordinates organ metabolism and blood supply, and it modulates immune responses. In the kidney it mediates the vascular response elicited by changes in NaCl concentration in the macula densa region of the nephron, thereby serving as an important regulator of GFR. To determine whether adenosine formation depends on extracellular nucleotide hydrolysis, we studied NaCl-dependent GFR regulation (tubuloglomerular feedback) in mice with targeted deletion of ecto-5'-nucleotidase/CD73 (e-5'NT/CD73), the enzyme responsible for adenosine formation from AMP. e-5'NT/CD73(-/-) mice were viable and showed no gross anatomical abnormalities. Blood pressure, blood and urine chemistry, and renal blood flow were not different between e-5'NT/CD73(+/+) and e-5'NT/CD73(-/-) mice. e-5'NT/CD73(-/-) mice had a significantly reduced fall in stop flow pressure and superficial nephron glomerular filtration rate in response to a saturating increase of tubular perfusion flow. Furthermore, whereas tubuloglomerular feedback responses did not change significantly during prolonged loop of Henle perfusion in e-5'NT/CD73(+/+) mice, a complete disappearance of the residual feedback response was noted in e-5'NT/CD73(-/-) mice over 10 minutes of perfusion. The contractile response of isolated afferent arterioles to adenosine was normal in e-5'NT/CD73(-/-) mice. We conclude that the generation of adenosine at the glomerular pole depends to a major extent on e-5'NT/CD73-mediated dephosphorylation of 5'-AMP, presumably generated from released ATP.
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PMID:Impairment of tubuloglomerular feedback regulation of GFR in ecto-5'-nucleotidase/CD73-deficient mice. 1534 76