Inhibition of proximal convoluted tubule transport by dopamine

Inhibition of proximal convoluted tubule transport by dopamine.BackgroundDopamine can produce a natriuresis and diuresis independent of changes in renal hemodynamics. However, previous studies have failed to demonstrate an inhibition of transport by dopamine in intact proximal convoluted tubules.MethodsRabbit proximal convoluted tubules were perfused in vitro with an ultrafiltrate-like solution and bathed in a serum-like albumin solution.ResultsIn the present study, the addition of 10-5m dopamine to the lumen or bath of proximal convoluted tubules perfused in vitro had no effect on transport. In proximal convoluted tubules, addition of 10-6m bath norepinephrine increased the rate of volume absorption from 0.65 ± 0.08 to 0.93 ± 0.08nl/mm · min (P < 0.01). Addition of 10-5m luminal dopamine in the presence of bath norepinephrine inhibited the rate of volume absorption to 0.72 ± 0.10nl/mm · min (P = 0.01). The inhibition in the rate of volume absorption by luminal dopamine in the presence of bath norepinephrine was completely blocked by the DA1 antagonist, SCH 23390. The DA1 agonist luminal 10-5m fenoldopam also inhibited volume absorption in the presence of bath norepinephrine, but the DA2 agonist luminal 10-5m quinpirole was without effect. Bath 10-5m dopamine had no effect on volume absorption in the presence of bath norepinephrine.ConclusionDopamine has no direct epithelial action on the proximal convoluted tubule. However, luminal dopamine antagonizes the stimulation in transport produced by norepinephrine. These studies suggest that luminal dopamine may play a role to modulate sodium transport in the presence of renal nerve activity

Combinatorial Variations on Cantor's Diagonal

We discuss counting problems linked to finite versions of Cantor's diagonal of infinite tableaux. We extend previous results of [2] by refining an equivalence relation that reduces significantly the exhaustive generation. New enumerative results follow and allow to look at the sub-class of the so- called bi-Cantorian tableaux. We conclude with a correspondence between Cantorian-type tableaux and coloring of hypergraphs having a square number of vertices

Origin of renal myofibroblasts in the model of unilateral ureter obstruction in the rat

Tubulo-interstitial fibrosis is a constant feature of chronic renal failure and it is suspected to contribute importantly to the deterioration of renal function. In the fibrotic kidney there exists, besides normal fibroblasts, a large population of myofibroblasts, which are supposedly responsible for the increased production of intercellular matrix. It has been proposed that myofibroblasts in chronic renal failure originate from the transformation of tubular cells via epithelial-mesenchymal transition (EMT) or from infiltration by bone marrow-derived precursors. Little attention has been paid to the possibility of a transformation of resident fibroblasts into myofibroblasts in renal fibrosis. Therefore we examined the fate of resident fibroblasts in the initial phase of renal fibrosis in the classical model of unilateral ureter obstruction (UUO) in the rat. Rats were perfusion-fixed on days 1, 2, 3 and 4 after ligature of the right ureter. Starting from 1day of UUO an increasing expression of alpha-smooth muscle actin (αSMA) in resident fibroblasts was revealed by immunofluorescence and confirmed by the observation of bundles of microfilaments and webs of intermediate filaments in the electron microscope. Inversely, there was a decreased expression of 5′-nucleotidase (5′NT), a marker of renal cortical fibroblasts. The RER became more voluminous, suggesting an increased synthesis of matrix. Intercellular junctions, a characteristic feature of myofibroblasts, became more frequent. The mitotic activity in fibroblasts was strongly increased. Renal tubules underwent severe regressive changes but the cells retained their epithelial characteristics and there was no sign of EMT. In conclusion, after ureter ligature, resident peritubular fibroblasts proliferated and they showed progressive alterations, suggesting a transformation in myofibroblasts. Thus the resident fibroblasts likely play a central role in fibrosis in that mode

Renal citrate metabolism and urinary citrate excretion in the infant rat

Renal citrate metabolism and urinary citrate excretion in the infant rat.BackgroundAlthough hypercalciuria has the same prevalence in children as adults, children rarely develop renal stones. This may be explained by a greater urinary citrate excretion in infants compared with adults. The present study examines the renal excretion of citrate and renal cortical citrate metabolism in infant and adult rats.MethodsAdult male and newly weaned infant rats were acclimated to metabolic cages and fed synthetic diets. Urine was collected after two days, and renal cortical citrate metabolism was assayed.ResultsInfant rats had a lower plasma [HCO3-] and higher plasma [K+] and had a fourfold higher urinary citrate:creatinine ratio and a twofold higher concentration of citrate in their urine compared with adult rats. This higher urinary citrate excretion was not due to a difference in renal proximal tubular Na/citrate cotransporter activity, nor renal cortical citrate synthase or ATP citrate lyase activities in infants as compared with adults. However, infant rat kidneys had significantly lower mitochondrial aconitase (m-aconitase) activity. Renal cortical citrate concentrations were comparable in infant and adult rats. Manipulation of plasma [K+] to adult levels did not affect the higher urinary citrate excretion in infant rats.ConclusionsUrinary citrate excretion in infant rats is greater than in adults but does not parallel tissue [citrate]. Thus, this higher urinary citrate is likely due to maturational differences in the proximal tubule, other than Na/citrate cotransport, that directly affect citrate transport

Renal citrate metabolism and urinary citrate excretion in the infant rat

Renal citrate metabolism and urinary citrate excretion in the infant rat.BackgroundAlthough hypercalciuria has the same prevalence in children as adults, children rarely develop renal stones. This may be explained by a greater urinary citrate excretion in infants compared with adults. The present study examines the renal excretion of citrate and renal cortical citrate metabolism in infant and adult rats.MethodsAdult male and newly weaned infant rats were acclimated to metabolic cages and fed synthetic diets. Urine was collected after two days, and renal cortical citrate metabolism was assayed.ResultsInfant rats had a lower plasma [HCO3-] and higher plasma [K+] and had a fourfold higher urinary citrate:creatinine ratio and a twofold higher concentration of citrate in their urine compared with adult rats. This higher urinary citrate excretion was not due to a difference in renal proximal tubular Na/citrate cotransporter activity, nor renal cortical citrate synthase or ATP citrate lyase activities in infants as compared with adults. However, infant rat kidneys had significantly lower mitochondrial aconitase (m-aconitase) activity. Renal cortical citrate concentrations were comparable in infant and adult rats. Manipulation of plasma [K+] to adult levels did not affect the higher urinary citrate excretion in infant rats.ConclusionsUrinary citrate excretion in infant rats is greater than in adults but does not parallel tissue [citrate]. Thus, this higher urinary citrate is likely due to maturational differences in the proximal tubule, other than Na/citrate cotransport, that directly affect citrate transport

Origin of renal myofibroblasts in the model of unilateral ureter obstruction in the rat

Tubulo-interstitial fibrosis is a constant feature of chronic renal failure and it is suspected to contribute importantly to the deterioration of renal function. In the fibrotic kidney there exists, besides normal fibroblasts, a large population of myofibroblasts, which are supposedly responsible for the increased production of intercellular matrix. It has been proposed that myofibroblasts in chronic renal failure originate from the transformation of tubular cells via epithelial–mesenchymal transition (EMT) or from infiltration by bone marrow-derived precursors. Little attention has been paid to the possibility of a transformation of resident fibroblasts into myofibroblasts in renal fibrosis. Therefore we examined the fate of resident fibroblasts in the initial phase of renal fibrosis in the classical model of unilateral ureter obstruction (UUO) in the rat. Rats were perfusion-fixed on days 1, 2, 3 and 4 after ligature of the right ureter. Starting from 1 day of UUO an increasing expression of alpha-smooth muscle actin (αSMA) in resident fibroblasts was revealed by immunofluorescence and confirmed by the observation of bundles of microfilaments and webs of intermediate filaments in the electron microscope. Inversely, there was a decreased expression of 5′-nucleotidase (5′NT), a marker of renal cortical fibroblasts. The RER became more voluminous, suggesting an increased synthesis of matrix. Intercellular junctions, a characteristic feature of myofibroblasts, became more frequent. The mitotic activity in fibroblasts was strongly increased. Renal tubules underwent severe regressive changes but the cells retained their epithelial characteristics and there was no sign of EMT. In conclusion, after ureter ligature, resident peritubular fibroblasts proliferated and they showed progressive alterations, suggesting a transformation in myofibroblasts. Thus the resident fibroblasts likely play a central role in fibrosis in that model

Role of fibroblast growth factor receptors 1 and 2 in the ureteric bud

AbstractFibroblast growth receptors (FGFRs) consist of four signaling family members. Mice with deletions of fgfr1 or fgfr2 are embryonic lethal prior to the onset of kidney development. To determine roles of FGFR1 and FGFR2 in the ureteric bud, we used a conditional targeting approach. First, we generated transgenic mice using the Hoxb7 promoter to drive cre recombinase and green fluorescent protein expression throughout ureteric bud tissue. We crossed Hoxb7creEGFP mice with mice carrying lox-p sites flanking critical regions of fgfr1 and/or fgfr2. Absence of fgfr1 from the ureteric bud (fgfr1UB−/−) results in no apparent renal abnormalities. In contrast, fgfr2UB−/− mice have very aberrant ureteric bud branching, thin ureteric bud stalks, and fewer ureteric bud tips. Fgfr2UB−/− ureteric bud tips also demonstrate inappropriate regions of apoptosis and reduced proliferation. The nephrogenic mesenchymal lineage in fgfr2UB−/− mice develops normal-appearing glomeruli and tubules, and only slightly fewer nephrons than controls. In contrast, fgfr2UB−/− kidneys have abnormally thickened subcapsular cortical stromal mesenchyme. Ultimately, fgfr2UB−/− adult kidneys are small and abnormally shaped or are hydronephrotic. Finally, there are no additional abnormalities in the fgfr1/2UB−/− kidneys versus the fgfr2UB−/− kidneys. In conclusion, FGFR2, but not FGFR1, appears crucial for ureteric bud branching morphogenesis and stromal mesenchyme patterning

Conditional expression of PfAP2-G for controlled massive sexual conversion in Plasmodium falciparum.

Malaria transmission requires that some asexual parasites convert into sexual forms termed gametocytes. The initial stages of sexual development, including sexually committed schizonts and sexual rings, remain poorly characterized, mainly because they are morphologically identical to their asexual counterparts and only a small subset of parasites undergo sexual development. Here, we describe a system for controlled sexual conversion in the human malaria parasite Plasmodium falciparum, based on conditional expression of the PfAP2-G transcription factor. Using this system, ~90 percent of the parasites converted into sexual forms upon induction, enabling the characterization of committed and early sexual stages without further purification. We characterized sexually committed schizonts and sexual rings at the transcriptomic and phenotypic levels, which revealed down-regulation of genes involved in solute transport upon sexual commitment, among other findings. The new inducible lines will facilitate the study of early sexual stages at additional levels, including multiomic characterization and drug susceptibility assays

Conditional expression of PfAP2-G for controlled massive sexual conversion in Plasmodium falciparum

--- - i: - Plasmodium falciparum content: - "Malaria transmission requires that some asexual parasites convert into sexual forms termed gametocytes. The initial stages of sexual development, including sexually committed schizonts and sexual rings, remain poorly haracterized, mainly because they are morphologically identical to their sexual counterparts and only a small subset of parasites undergo sexual development. Here, we describe a system for controlled sexual conversion in the human malaria parasite " - ", based on conditional expression of the PfAP2-G transcription factor. Using this system, ~90 percent of the parasites converted into sexual forms upon induction, enabling the characterization of committed and early sexual stages without further purification. We characterized sexually committed schizonts and sexual rings at the transcriptomic and phenotypic levels, which revealed down-regulation of genes involved in solute transport upon sexual commitment, among other findings. The new inducible lines will facilitate the study of early sexual stages at additional levels, including multiomic characterization and drug susceptibility assays.