The distribution of p-aminohippuric acid in rat kidney slices. I. Tubular localization

Wedeen, Richard P.; Weiner, Brian C.

doi:10.1038/ki.1973.33

Cited by 61 publications

(40 citation statements)

References 41 publications

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“…It can be hypothesized that the cellular compartment crossed by the amine before reaching the perifusate is the very same in which dopamine is synthesized; however, this would imply that the amine would be taken up into the original cellular structure, after being released. Considering that the luminal cell border has been shown not to take up dopamine (Chan, 1976) and this cell border has been found to be collapsed when renal slices are used (Wedeen & Weiner, 1973), it might then be suggested that the released dopamine would be taken up into tubular epithelial cells through the basolateral membrane. This hypothesis might explain why the proportion of DOPAC to dopamine is significantly higher in the perifusate than that found in the tissues and would also support the results presented here on the influence of selective and non selective MAO inhibitors in the outflow levels of dopamine and DOPAC.…”

Section: Discussionmentioning

confidence: 99%

Effect of type A and B monoamine oxidase selective inhibition by Ro 41–1049 and Ro 19–6327 on dopamine outflow in rat kidney slices

Pestana

Soares‐da‐Silva

1994

British J Pharmacology

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1 The influence of pargyline and of selective inhibitors of type A and B monoamine oxidase (MAO), Ro 41-1049 and Ro 19-6327 respectively, on the outflow of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) in slices of rat renal cortex loaded with exogenous L-3,4-dihydroxyphenylalanine (L-DOPA) was examined. Dopamine and DOPAC in the tissues and in the effluent were assayed by means of h.p.l.c. with electrochemical detection. 2 The levels of newly-formed dopamine and DOPAC in the perifusate decreased progressively with time. In control conditions, DOPAC/dopamine ratios in the perifusate were 3 to 5 fold those in the tissue and were found to increase progressively with time. The addition of pargyline (100 ItM), produced a marked decrease in the outflow levels of DOPAC (45 to 54% reduction) and significantly increased the levels of dopamine in the effluent (102 to 158% increase); DOPAC/dopamine ratios in the perifusate remained stable throughout the perifusion and were similar to those found in the tissues. The addition of the MAO-A inhibitor Ro 41-1049 to the perifusion fluid also significantly decreased DOPAC outflow (41% to 54% reduction) and increased dopamine outflow (19% to 80% increase). In the presence of Ro 41-1049 DOPAC/dopamine ratios in the perifusate were lower (P<0.01) than in controls; in contrast with the effect of pargyline, this ratio was found to increase (P < 0.01) throughout the perifusion period. Ro 19-6327 did not reduce the outflow of DOPAC, but significantly increased (by 40-60%) that of dopamine. In the presence of Ro 19-6237, the proportion of DOPAC to dopamine in the perifusate was similar to that of controls and significantly increased throughout the perifusion; however, this increase was less than that observed in the control group. 3 When benserazide (50 JAM) was added to the perifusion fluid, the levels of both dopamine and DOPAC in the effluent were similar to those observed in the absence of benserazide. However, in the presence of benserazide, DOPAC/dopamine ratios in the perifusate did not increase with time. In conditions of decarboxylase inhibition, the effects of pargyline, Ro 41-1049 and Ro 19-6327 on dopamine and DOPAC outflow were less pronounced than in experiments conducted in the absence of benserazide. 4 In conclusion, the results presented here show that the fraction of newly-formed dopamine which leaves the compartment where the synthesis has occurred is a constant source for deamination into DOPAC. The results provide evidence favouring the view that MAO-A is the main form of the enzyme involved in this process; however, the data described here suggest that dopamine would also have access to MAO-B.

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Section: Discussionmentioning

confidence: 99%

Effect of type A and B monoamine oxidase selective inhibition by Ro 41–1049 and Ro 19–6327 on dopamine outflow in rat kidney slices

Pestana

Soares‐da‐Silva

1994

British J Pharmacology

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“…1). Greater uptake for smaller slices is an expected observation (15,29 Concentration-dependent uptake. Taurine uptake at solved by the method of Neal (27) to obtain corrected steady state is influenced by the extracellular concentration (Fig.…”

Section: Introductionmentioning

confidence: 99%

“…Our purpose was to determine the contribution of urine trapped in uncollapsed nephrons to the estimate of tissue taurine. This artefact has been shown to be of some significance (10), since tubular urine is squeezed from the tissue during preparation of slices (15), but not in the preparation of whole cortex homogenate. Further precaution was taken by permitting the slices to leach on filter paper soaked in 0.9% NaCl at 4VC for 5 min as the tubule lumen collapsed.…”

Section: Introductionmentioning

confidence: 99%

“…We have compared our data for in vivo reclamation of taurine with our findings in vitro, obtained from small kidney cortex slices. Occlusion of the luminal membranes and selective exposure of basilar membranes of absorbing epithelium to substrate in the medium, which are constraints imposed by the slice technique (15), have been put to advantage in this investigation. Moreover, we have found that taurine is virtually an inert substance with respect to its renal metabolism in kidney, so that isotopic tracer studies informed us specifically about uptake characteristics.…”

Section: Introductionmentioning

confidence: 99%

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Localization of the membrane defect in transepithelial transport of taurine by parallel studies in vivo and in vitro in hypertaurinuric mice.

Chesney¹,

Scriver²,

Mohyuddin³

1976

J. Clin. Invest.

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A B S T R A C T We investigated the mechanism of taurinuria in three inbred strains of mice: A/J, a normal taurine excretor (taut+) ; and two hypertaurinuric (taut) strains, C57BL/6J and PRO/Re. Plasma taurine is comparable in the three strains (-0.5 mM), but taurinuria is 10-fold greater in tau'-animals. Fractional reabsorption of taurine is 0.967±0.013 (mean±SD) in A/J); and 0.839±0.08 and 0.787+0.05 in C57BL/6J and PRO/Re, respectively. Taurine concentration in renal cortex intracellular fluid (free of urine contamination) is similar in the three strains. Taurine reabsorption is inhibited by fi-alanine, in taut`and taut' strains. These in vivo findings reveal residual taurine transport activity in the taut' phenotype and no evidence for impaired efflux at basilar membranes as the cause of impaired taurine reabsorption.Cortex slices provide information about uptake of amino acids at the antiluminal membrane. Taurine behaves as an inert metabolite in mouse kidney cortex slices. Taurine uptake by slices is active and, at < 1 mM, is greater than normal in taut' slices. Concentration-dependent uptake studies reveal more than one taurine carrier in taut+ and taut' strains. The apparent K. values for uptake below 1 mM are different in taut' and taut`slices (-0.2 mM and 0.7 mM, respectively); the apparent K. values above 1 mM taurine are similar in taut and taut' slices. Efflux from slices in all strains is the same (0.0105-0.0113 Amol min-lfg-1 wet wt), but taut' tissue retains about 10% more radioactivity over the period of efflux. P-Alanine is actively metabolized in mouse kidney.

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“…nantly at the basolateral membrane (20,26). Therefore, in vivo (reabsorption) and in vitro (uptake) studies may not inform us about the same topologic process of uptake.…”

Section: Amino Acid Reabsorption In Human Kidneymentioning

confidence: 99%

Ontogeny of Amino Acid Reabsorption in Human Kidney. Evidence from the Homozygous Infant with Familial Renal Iminoglycinuria for Multiple Proline and Glycine Systems

Lasley

Scriver

1979

Pediatr Res

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Summaryadditional transport process(es) in the renal tubule, perhaps one with a preference for iminoacids and another with preference for seven infants French Canadim9' Our J e~s h , glycine (16,24). Since net reabsorption is determined to a great and one Greek) with massive selective hyperiminoglycinuria (proline, hydroxyproline, and glycine) were detected by urine screening extent by brush border membrane transport activity of the proxiin the second week of life. Follow-up investigations and family ma1 tubule (19,20), in this instance a benign mutation appears to studies revealed that each subject had a benign condition, frmilial be a useful probe, revealing the presence of more than one renal iminoglycinuria, an autosomal recessive condition. transport system serving iminoacids and glycine in that membrane of tubular epithelial cells. In this report, we have used the occurThe family studies ( Table 1 and Fig. 1) indicate the presence of rence of ontogeny and mutation together to examine this possiat least two different mutant alleles segregating in this small group bility in the human infant. of probands. Homozygotes of two forms and one genetic compound were identified.Quantitative studies revealed normal concentrations of proline (Table 2). Frat-azi Jewish, and one Greek), each with exceptional iminoglycinuria, tional excretion (c&ccR) of both proline and glyche in the were discovered in the second week of life by the urine screening probands was far in excess of that expected for the noranal program of the Quebec Network of Genetic ~e d i c i n e (10, 25). postnatal infant; F E~ and F E~~~ 100% of the filtered After follow-up qualitative studies had confirmed the presence load on occasion (~i~. 4). A of maturing reab-of persistent massive iminoglycinuria, each infant was admitted, sorptive activity was apparent in the proband group. probe with informed consent, as a day patient to the Clinical Investigareabsorption earlier than glycine reabsorption in the tion Unit at the Montreal Children's Hospital. More than one homozygotes (and the genetic compound) as it does in the normal quantitative study was performed during the first year of life in infants (Fig. 5).five of the patients (the probands for pedigrees 1, 2, 3, 4, and 6) Our fmdmgs suggest that three gene products serve net tubular and repeat qualitative studies were possible in six (the aforemenreabsorption of imino acids and glycine in human kidney. one, tioned probands plus proband 5). Family studies confirmed the affected by mutation in our patients, is responsible for a shared hereditary nature of the condition in all seven probands. *ansport activity; a second with preference for proline, and not For quantitative studies, a timed morning urine wllection was by the mutation, has an schedule of postnatal obtained in the fasting state. Glucose-water (5% w/v) was offered maturation; and a third with preference for glyche, also not to increase the urine rate during the by the mutation, has a schedule of maturation. period which lasted about 3 hr. Ur...

show abstract

The distribution of p-aminohippuric acid in rat kidney slices. I. Tubular localization

Cited by 61 publications

References 41 publications

Effect of type A and B monoamine oxidase selective inhibition by Ro 41–1049 and Ro 19–6327 on dopamine outflow in rat kidney slices

Effect of type A and B monoamine oxidase selective inhibition by Ro 41–1049 and Ro 19–6327 on dopamine outflow in rat kidney slices

Localization of the membrane defect in transepithelial transport of taurine by parallel studies in vivo and in vitro in hypertaurinuric mice.

Ontogeny of Amino Acid Reabsorption in Human Kidney. Evidence from the Homozygous Infant with Familial Renal Iminoglycinuria for Multiple Proline and Glycine Systems

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