Localization of urate transport in the nephron of mongrel and Dalmatian dog kidney

1959 ◽  
Vol 197 (3) ◽  
pp. 601-603 ◽  
Author(s):  
Richard H. Kessler ◽  
Klaus Hierholzer ◽  
Ruth S. Gurd
Keyword(s):  
Flow Analysis ◽  
Secretory Activity ◽  
Distal Segment ◽  
Free Flow ◽  
Proximal Segment ◽  
Urate Transport ◽  
Dog Kidney ◽  
Stop Flow ◽  
Urate Reabsorption ◽  
Dalmatian Dog

Localization of urate transport within the nephrons of mongrel and Dalmatian dogs was studied by stop-flow analysis. In mongrel dogs urate concentrations and clearance ratios were lowest in the segment in which PAH was secreted. Urate clearance ratios of 0.7 in free-flow samples were reduced to about 0.3 in stop-flow samples from the proximal segment. In the distal segment urate clearance ratios did not differ significantly from ratios obtained in free-flow. Probenecid, in doses sufficient to block PAH secretion, inhibited urate reabsorption thereby increasing urate clearance. In contrast to these findings with mongrel dogs, the Dalmatians exhibited weak but definite urate secretion within the proximal segment. The action of probenecid in this strain of dogs was to stop all proximal secretory activity for urate thereby reducing urate clearance. It was suggested that mongrel and Dalmatian dogs transport urate by systems that are identical except for direction of urate movement.

Tubular secretion of urate in the dog

1960 ◽  
Vol 199 (6) ◽  
pp. 1199-1204 ◽  
Author(s):  
Ts'ai Fan Yü ◽  
Lawrence Berger ◽  
Sherman Kupfer ◽  
Alexander B. Gutman
Keyword(s):  
Distal Segment ◽  
Tubular Secretion ◽  
Tubular Reabsorption ◽  
Proximal Segment ◽  
Clearance Studies ◽  
Mongrel Dog ◽  
Active Processes ◽  
Stop Flow ◽  
Urate Reabsorption ◽  
Urate Secretion

Clearance studies under appropriate conditions of urate loading and osmotic diuresis yielded Curate/GFR ratios > 1.10 in both Dalmatian and non-Dalmatian dogs, indicating tubular secretion of urate. In the purebred Dalmatian, stop-flow studies (U/Purate: U/Pcreatinine ratios) localized peak net urate secretion to the proximal segment, with a second, lesser peak in the distal segment. Both peaks were abolished by probenecid and, in massive dosage, by PAH, yielding ratios < 1. In the mongrel dog, stop-flow studies showed maximal net tubular reabsorption of urate in the proximal segment, peak net tubular secretion of urate in the distal segment. Proximal urate secretion was not demonstrated but may have been masked by preponderant urate reabsorption. It is suggested that, as in man, renal regulation of urate excretion in the dog involves glomerular filtration, tubular reabsorption (deficient but still demonstrable in the Dalmatian) and tubular secretion (ordinarily masked by preponderant reabsorption in the non-Dalmatian). Both reabsorption and secretion of urate in the dog appear to be effected largely by ‘active’ processes.

Stop-flow analysis of creatinine excretion in the dog

1962 ◽  
Vol 203 (6) ◽  
pp. 980-984 ◽  
Author(s):  
Robert E. Swanson ◽  
Ali A. Hakim
Keyword(s):  
Creatinine Clearance ◽  
Competitive Inhibition ◽  
Flow Analysis ◽  
High Plasma ◽  
Free Flow ◽  
Inulin Clearance ◽  
Plasma Creatinine ◽  
Clearance Ratio ◽  
Creatinine Concentration ◽  
Stop Flow

Urinary excretion patterns of creatinine and inulin under stop-flow conditions in male mongrel dogs were compared. Evidence for a weak creatinine secretory mechanism at the proximal tubule level include the following: 1) Exogenous creatinine in the stop-flow samples appears prior to inulin when both are injected midway during a 10-min ureteral clamping period. 2) The ratio of creatinine/inulin U/P values (creatinine clearance ratio) shows a peak and a distribution coextensive with PAH/inulin clearance ratios. 3) Self-depression of the peak stop-flow creatinine clearance ratio was obtained at high plasma creatinine concentrations. 4) High plasma p-aminohippuric acid levels depressed the free-flow and peak stop-flow creatinine clearance ratios and, conversely, high plasma creatinine concentration depressed free-flow and peak stop-flow PAH clearance ratios (competitive inhibition). 5) Probenecid reduced free-flow and peak stop-flow creatinine clearance ratios (creatinine secretory mechanism blocked). The mean free-flow creatinine/inulin clearance ratios in 44 clearance periods was 1.2±0.1 (sd), compared to the peak stop-flow ratio of 1.8±0.4 (sd) (N = 20) at plasma creatinine concentrations less than 20 mg/100 ml.

Localization of action of chlorothiazide in the nephron of the dog

1959 ◽  
Vol 196 (6) ◽  
pp. 1346-1351 ◽  
Author(s):  
Richard H. Kessler ◽  
Klaus Hierholzer ◽  
Ruth S. Gurd ◽  
Robert F. Pitts
Keyword(s):  
Sodium Chloride ◽  
Carbonic Anhydrase ◽  
Ion Transport ◽  
Distal Segment ◽  
Proximal Segment ◽  
Inhibitory Effects ◽  
Stop Flow

Localization of the actions of chlorothiazide in dogs has been studied by the ‘stop-flow’ technique. The compound interfered with the reabsorption within the proximal segment of a portion of the filtered sodium chloride. In this activity it exhibited effects qualitatively similar to those of chlormerodrin, an organic mercurial diuretic. In addition, chlorothiazide diminished H+ and NH4+ excretion while augmenting K+ secretion within the distal segment. These are typical of the carbonic anhydrase inhibitory effects observed previously with acetazoleamide and presented in this study with dichlorphenamide. Probenecid blocked the proximal secretion of chlorothiazide but did not alter its actions on ion transport.

Renal reabsorption of amino acids

1962 ◽  
Vol 203 (5) ◽  
pp. 891-896 ◽  
Author(s):  
Marian Ruszkowski ◽  
Cizesław Arasimowicz ◽  
Jan Knapowski ◽  
Jan Steffen ◽  
Krystyna Weiss
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Transport Mechanism ◽  
Flow Analysis ◽  
Proximal Segment ◽  
Renal Tubules ◽  
Basic Amino Acids ◽  
Tubular Transport ◽  
The Common ◽  
Stop Flow

Using the method of stop flow analysis an attempt was made to localize the process of amino acid reabsorption in the nephron of the dog. Special attention was given to the group of basic amino acids and cystine believed to share a common tubular transport mechanism. The evidence obtained in this study points clearly to the proximal segment as the site of intensive reabsorption of all amino acids investigated. During the infusion of arginine, lysine or ornithine, an increased excretion of two remaining basic amino acids plus cystine was observed, as a rule. Successful attempts were made to infuse cystine intravenously. The results of these experiments did provide the missing link for the hypothesis derived by Dent and Rose ( Quart. J. Med. 20: 205, 1951) concerning the common transport mechanism of arginine, ornithine, lysine, and cystine in the renal tubules. The functional cystinuria, which can be induced by saturating the common reabsorptive pathway with each of the above-mentioned amino acids, is fully reversible.

Stop-flow analysis of tubular transport of uric acid in rabbits

1964 ◽  
Vol 207 (6) ◽  
pp. 1265-1272 ◽  
Author(s):  
E. C. Beechwood ◽  
W. O. Berndt ◽  
Gilbert H. Mudge
Keyword(s):  
Uric Acid ◽  
Flow Analysis ◽  
Distal Tubule ◽  
Free Flow ◽  
Transport Systems ◽  
Clearance Ratio ◽  
Renal Handling ◽  
Pronounced Increase ◽  
Secretory Transport ◽  
Stop Flow

Various physiological and pharmacological aspects of the renal handling of uric acid have been investigated. In the majority of rabbits the free-flow urate-to-inulin clearance ratio was found to be less than 1, although some animals (about 20%) demonstrated net secretion. Despite the predominance of net reabsorption under free-flow conditions, the usual stop-flow pattern showed only a proximal secretory peak. No distal tubular activity was evident under any of the experimental circumstances studied. The administration of chlorothiazide, lactic acid, creatinine, or pyrazinoic acid caused a pronounced increase in the proximal secretory peak. Probenecid produced a depression of the secretory peak resulting in a net reabsorptive dip. This reversal of proximal tubular activity is taken as evidence for the presence of both secretory and reabsorptive mechanisms. The following phenomena have been found to be involved in the renal handling of uric acid by the rabbit: 1) filtration of urate at the glomerulus; 2) proximal reabsorptive and secretory transport systems which are drug sensitive; and 3) relative impermeability of the distal tubule to urate.

Influence of inorganic electrolytes and ouabain on uric acid transport

1965 ◽  
Vol 208 (4) ◽  
pp. 642-648 ◽  
Author(s):  
W. O. Berndt ◽  
E. C. Beechwood
Keyword(s):  
Uric Acid ◽  
Organic Acids ◽  
Potassium Concentration ◽  
Flow Analysis ◽  
Rabbit Kidney ◽  
Kidney Cortex ◽  
Acid Transport ◽  
Acid Accumulation ◽  
Stop Flow ◽  
Urate Reabsorption

The importance of certain inorganic electrolytes in the transport of some organic acids by the kidney has been demonstrated. The present study was undertaken to evaluate further the transport characteristics for uric acid. Slices of rabbit kidney cortex were found to accumulate urate with a dependency on the medium potassium concentration. At 5 mm potassium the urate uptake was about 50% of maximum, with optimal accumulation above 10–40 mm potassium. Rubidium or cesium were found to substitute successfully for potassium; both substances permitted better uric acid accumulation than did potassium. Removal of sodium from the medium to concentrations as low as 65 mm did not influence urate uptake. At 15 mm sodium the urate accumulation was markedly depressed. Ouabain was found to depress urate uptake. The inhibition produced by this substance could be reversed by elevation of the medium potassium. Stop-flow analysis on the rabbit indicated that ouabain increased the proximal secretory peak for uric acid. On the basis of experiments where ouabain and probenecid were administered together, it was possible to attribute the action of ouabain to blockade of urate reabsorption.

Demonstration of distal tubular flux of phosphorus using modified stop-flow analysis

Metabolism ◽  
1966 ◽  
Vol 15 (6) ◽  
pp. 482-491 ◽  
Author(s):  
Bernard B. Davis ◽  
Laurence H. Kedes ◽  
James B. Field
Keyword(s):  
Flow Analysis ◽  
Stop Flow

Net urate reabsorption in the Dalmatian coach hound with a note on automated measurement of urate in species with low plasma urate

1982 ◽  
Vol 60 (12) ◽  
pp. 1499-1504 ◽  
Author(s):  
B. Moulin ◽  
P. Vinay ◽  
N. Duong ◽  
A. Gougoux ◽  
G. Lemieux
Keyword(s):  
Glomerular Filtration Rate ◽  
Creatinine Clearance ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Progressive Reduction ◽  
Clearance Ratio ◽  
Plasma Urate ◽  
Urate Reabsorption ◽  
Dalmatian Dog ◽  
Pyrazinoic Acid

A progressive reduction of renal blood flow and glomerular filtration rate induced by the stepwise clamping of a Goldblatt clamp increases the urate over creatinine clearance ratio from 1.2 to 1.9 in normal urate-secreting Dalmatian dogs. These clearance data support the existence of a predominant postreabsorptive secretory flux of urate in the normal Dalmatian dog. In contrast, in Dalmatians loaded with pyrazinoic acid which suppresses urate secretion, net reabsorption of urate is unmasked and the urate over creatinine clearance ratio decreases with the progressive reduction in glomerular filtration rate (down to 0.44). It is concluded that the net reabsorption of urate measured by conventional clearance techniques after pharmacologic depression of the urate secretory flux probably reflects true urate reabsorption in the nephron of this species.

Stop-flow analysis in man

Metabolism ◽  
1966 ◽  
Vol 15 (12) ◽  
pp. 1076-1083 ◽  
Author(s):  
J. Jahnecke ◽  
J. Sökeland ◽  
A.W. Schmidt ◽  
F. Krück
Keyword(s):  
Flow Analysis ◽  
Stop Flow

CONGENITAL MEGACOLON

PEDIATRICS ◽  
1950 ◽  
Vol 5 (5) ◽  
pp. 791-798
Author(s):  
JOSEPH A. RITTER ◽  
HERBERT R. HAWTHORNE ◽  
HARRY N. METZGER
Keyword(s):  
Surgical Treatment ◽  
Distal Segment ◽  
Proximal Segment ◽  
Functional Improvement ◽  
Congenital Megacolon ◽  
Preferential Choice

Congenital megacolon of the obstructive type, currently attributed to agenesis of the intramural plexuses in the contiguous distal segment, is amenable to surgical treatment. Resection of either the distal neurogenically obstructive segment or the dilated proximal segment, contrastingly different procedures, results in anatomic and functional improvement. Three cases, herein reported, treated by resection of the dilated segment, demonstrate that the preferential choice of resection of the neurogenically obstructive segment may be on an equivocal physiologic basis. The new operations developed for eliminating the neurogenically obstructive segment appear to be an advancement in surgical technic.

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