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PubMed1993

Amino acid flux across the gastrointestinal tract and liver of calves.

Fluxes of peptide and of free AA in plasma and blood cells were quantified across the gastrointestinal tract and liver of six growing Holstein steers (136 kg). Calves were fed hourly, and blood was obtained simultaneously from the aorta, protal vein, and hepatic vein cannulas on 1 d between d 9 and 12 postsurgery and again following 72 h without feed. Blood flow was determined by p-aminohippuric acid infusion. Peptide AA accounted for the greatest concentration of AA in arterial blood of all calves. There was a net flux of free AA in plasma across the tract, and lack of feed reduced the magnitude of the flux. Glutamine and glutamate were the only free AA in plasma with a negative flux across the tract in fed calves. Alanine accounted for over 14% of the total tract flux of free AA in plasma of fed calves. Hepatic removal of free AA in plasma increased after feed deprivation. Flux of free AA in blood cells was negative across the tract of fed calves but to a lesser extent in unfed calves. The hepatic flux of free AA in blood cells offset the negative tract flux, thus resulting in no net splanchnic output of free AA in blood cells by calves. Peptide AA flux across the tract was 2.5 times (fed) to 7.2 times (unfed) greater than free AA flux. Net splanchnic output of peptide AA was 7 times the magnitude (738 vs. 92 g/d) of the net splanchnic output of free AA in plasma. Peptides with molecular mass from 500 to 1500 Da accounted for the largest flux of peptide AA across the tract. Quantitatively, peptides appeared to be involved extensively in interorgan transport and may be a substantial form of absorbed AA in calves.

Alanine↗
PubMed1991

Potential contribution of absorbed volatile fatty acids to whole-animal energy requirement in conscious swine.

Chronic cannulas were placed in the hepatic portal vein, ileal vein, and carotid artery in seven crossbred growing gilts trained to consume once daily 1.2 kg of a 16% CP corn-soybean meal diet. Eleven days after surgery, each pig (37.4 kg BW) was placed in an open-circuit calorimeter and its cannulas were connected to a system for determining portal absorption of nutrients. The whole-animal heat production and net portal absorption of gut VFA were measured simultaneously for 12 h after the pig was fed 1.2 kg of feed. Plasma concentrations of VFA, including acetic, propionic, isobutyric, butyric, isovaleric, and valeric acids, in portal and arterial samples were determined by gas chromatography after a cleanup by ion-exchange chromatography. The net portal absorption of VFA was calculated by multiplying the porto-arterial plasma concentration difference of the VFA by portal vein plasma flow. Plasma flow was estimated by the indicator-dilution technique using p-aminohippuric acid as the indicator. The energy value of absorbed VFA was the sum of products of each individual VFA multiplied by its corresponding value of the heat of combustion. The mean hourly energy value of absorbed VFA during the 12-h postprandial period was .65 +/- .03 kcal.h-1.kg BW-1. The mean hourly whole-animal heat production was 2.70 +/- .04 kcal.h-1.kg BW-1. Thus, in our 37.4-kg pigs, which were trained to consume 1.2 kg of a 16% CP corn-soybean meal diet once daily, the gut VFA absorbed into the portal vein could contribute 23.8 +/- 1.1% to whole-animal heat production if all of the absorbed VFA were combusted to CO2.

Absorption↗
PubMed2003

Drug-induced Fanconi's syndrome.

Fanconi's syndrome (FS) was first described by Lignac in 1924. Associated with numerous varieties of inherited and acquired conditions, FS is characterized by a generalized transport defect in the proximal tubules, leading to renal losses of glucose, phosphate, calcium, uric acid, amino acids, bicarbonates, and other organic compounds. Cardinal symptoms of the syndrome are hyperaminoaciduria, glucosuria in the face of a normal serum glucose level, and phosphate wasting. Other symptoms may be associated, such as defects in bicarbonate reabsorption; renal acidification; urate reabsorption; urinary concentration; potassium conservation; reabsorption of sodium, calcium, and low-molecular-weight proteins; and secretion of p-aminohippuric acid. Acquired renal tubular defects resulting in FS also have been described in association with many exogenous agents, whether administered or accidentally ingested. This review concentrates on drug-induced FS.

Alcoholism↗
PubMed1985

Avian renal responses to oxidized and nonoxidized bPTH(1-34).

The hypotensive, hypercalcemic, and hyperphosphaturic responses to bovine synthetic 1-34 amino acid parathyroid hormone [bPTH(1-34)] were simultaneously evaluated in anesthetized laying hens, and compared to the same responses to oxidized (0.3% hydrogen peroxide) bPTH(1-34) prepared from the same commercial batch of hormone. The oxidized and nonoxidized hormones were administered intravenously into separate groups of animals, which were also receiving a constant intravenous infusion of inulin and p-aminohippuric acid (PAH) to serve as renal clearance test markers. bPTH(1-34) caused a 33.25 +/- 7.05 mm Hg decrease in mean arterial blood pressure. The corresponding change in response to the oxidized hormone preparation was a 10.75 +/- 1.49 mm Hg decrease, a significant reduction in hypotensive activity compared to the intact hormone. In contrast, oxidation had no influence on the hypercalcemic or hyperphosphaturic (relative clearance of phosphate, CPO4/CIn) responses to bPTH(1-34), both preparations causing significant and parallel increases in these variables. Both hormone preparations also caused increases in urine flow rate, GFR, CPAH, CCa/CIn, CK/CIn, CNa/CIn, and urine pH. However, on the basis of percentage change from the respective control periods, only CNa/CIn and urine pH showed significant differences between the two hormone preparations, with the intact hormone causing greater natriuresis and urine alkalinization than the oxidized hormone. The failure of peroxide oxidation to significantly affect the renal hyperphosphaturic response to bPTH(1-34) in chickens contrasts with results reported on mammalian species, and may be related to differences in the mechanism of renal phosphate transport between these groups.

Animals↗
PubMed1983

Renal tubular secretion of piretanide and its effects on electrolyte reabsorption and tubuloglomerular feedback mechanism.

Piretanide [HOE 118; 4-phenoxy-3-(1-pyrrolidinyl)-5-sulfamoxylbenzoic acid] is a new diuretic with a saluretic effect similar to that of furosemide. The present experiments were undertaken to investigate if transport of piretanide into the tubular lumen determines the diuretic response and what effect piretanide has on the tubuloglomerular feedback control and loop of Henle electrolyte transport. To study the first question, five healthy subjects were investigated. Piretanide, inulin and p-aminohippuric acid were continuously infused. After equilibration, 1 g of probenecid was given which reduced the tubular secretion of piretanide to one-sixth of control level. The reduction in diuresis was 41.4% while it was 59.5, 63.9 and 45.8% for the urinary excretion of chloride, sodium and potassium, respectively. In a second series of experiments in rats a proximal tubular stop-flow pressure response at increased distal delivery of fluid was measured when Ringer's solution, Ringer's solution plus furosemide (10(-4) M) or bumetanide (5 X 10(-5) M) or piretanide (10(-4) M and 5 X 10(-5) M) was added to the tubular perfusion solution. The results indicate that the feedback could be completely blocked by any of these diuretics. The fluid absorption in the loop of Henle was studied in separate experiments and the addition of piretanide (10(-4) M) greatly reduced chloride and absolute fluid absorption from this nephron segment. The present results indicate that tubular secretion of piretanide is important for the diuretic response and that piretanide inhibits the fluid absorption in the loop of Henle and the tubuloglomerular feedback control which would otherwise blunt the diuretic response with a reduction in glomerular filtration rate.

Diuretics↗
PubMed1996

Effect of intraruminal propionic acid infusion on metabolism of mesenteric- and portal-drained viscera in growing steers fed a forage diet: II. Ammonia, urea, amino acids, and peptides.

This experiment investigated the effect of intraruminal infusion of propionic acid on the net flux of nitrogenous compounds across the mesenteric- (MDV) and portal-(PDV) drained viscera of seven Friesian steers, average BW 127 kg (SEM 4.6), fed a grass-pellet diet. Each received by random allocation 0 (control), .5, or 1.0 mol of propionic acid/d for 7 d. Blood flow in mesenteric and portal veins was determined by downstream dilution of p-aminohippuric acid in order to determine net appearance rates across the gastrointestinal tissues. Net urea and ammonia flux was unaffected by propionic acid supply. Circulating plasma free amino acid concentrations were increased (P < .05) by propionic acid infusion (2,235, 2,428, and 2,427, error mean square [EMS] 44,370 microM, for control, .5, and 1.0 mol of propionic acid/d, respectively). Net amino acid flux rates were increased at the highest rate of propionic acid infusion across MDV and PDV (4.66, 3.69, and 6.11, EMS 2.98 mol/d for MDV [P < .05] and 2.98, 2.45, and 3.73, EMS 1.69 mol/d for PDV [P < .10] for control, .5, and 1.0 mol of propionic acid/d respectively). Positive venous-arterio concentration differences for peptide-bound amino acids (PBAA) across the MDV and PDV indicated net appearance across the gastrointestinal tissues, but this was not affected by propionic acid infusion. The data show that amino acid flux across postruminal tissues can be influenced by ruminal propionic acid supply and that this does not affect PBAA appearance.

Amino Acids↗
PubMed2000

Portal recovery of short-chain fatty acids infused into the temporarily-isolated and washed reticulo-rumen of sheep.

The present study was undertaken to study the metabolism of short-chain fatty acids (SCFA) by the reticulo-ruminal epithelium and the portal-drained viscera (PDV) under in vivo conditions with no interference from the metabolism of the rumen microbes. The technique of temporary isolation of the reticulo-rumen was applied to wethers implanted with catheters in a mesenteric artery, the hepatic portal vein and the right ruminal vein. Portal blood flow was measured by downstream dilution of p-aminohippuric acid; the PDV uptake of arterial acetate, as well as the whole-body irreversible loss rate (ILR) of acetate, was estimated by [2-(13)C]acetate infusion into the right ruminal vein. The sheep were maintained with a bicarbonate-buffered solution of SCFA in the reticulo-rumen along with continuous intraruminal infusion of SCFA for 4 h. The portal appearance of SCFA of non-reticulo-ruminal origin was estimated before and after the infusion protocol. Of the acetate absorbed by the sheep, 89 (SE 5), 109 (SE 7) and 101 (SE 7)% was recovered as portal net appearance of acetate, portal net appearance of acetate corrected for PDV uptake of arterial acetate and increase in the ILR of acetate respectively. Of the propionate, isobutyrate, butyrate, isovalerate and valerate absorbed by the sheep, 95 (SE 7), 102 (SE 9), 23 (SE 3), 48 (SE 5) and 32 (SE 4)% respectively was recovered as portal net appearance. In contrast to current concepts, the present study showed that the reticulo-ruminal epithelium metabolizes none (or only a small proportion) of the acetate and propionate absorbed from the rumen. This observation could lead to the more efficient use of results obtained with multi-catheterized animals to quantify the net metabolite output of the rumen microbes.

Acetates↗
PubMed1976

Inhibition of in vitro concentrative prostaglandin accumulation by prostaglandins, prostaglandin analogues and by some inhibitors of organic anion transport.

1. Incubation of rabbit choroid plexus, anterior uvea (iris-ciliary body complex) or slices of kidney cortex in a medium containing tritium-labelled prostaglandin F(2alpha) ([3H]PGF(2alpha) or E1 ([3H]PGE1) results in a four- to thirteenfold concentrative accumulation of 3H activity. 2. Addition of PGF(2alpha, PGF(1) or PGA(1), any one of five PG analogues or a PG precursor, arachidonic acid, at a concentration of 10(-4) M reduced the active accumulation of [3H]PGs by 47-97%. Octanoic acid, at the same concentration, had only a moderate effect on the choroid plexus and no significant inhibitory effect on [3H]PFG(2alpha) accumulation by anterior uvea or kidney cortex. 3. Inhibition was also obtained with 2 mM iodoacetate (under anaerobic conditions) and with 10(-4) M diploretin phosphate, probenecid, iodipamide, indomethacin or dinitrophenol. Perchlorate (10(-4) M) and iodide (10(-4) or 10(-3) M) had no inhibitory effect while 10(-4) M p-aminohippuric acid had a significant inhibitory effect on the kidney cortex at a concentration of 10(-4) M and on the anterior uvea at 10(-3) M. 4. It is concluded that the apparent carrier mediated PG transport systems of the choroid plexus, anterior uvea and kidney cortex are not related to the iodide transport system, but may represent a subcomponent of the iodipamide transport system of these tissues. 5. These results suggest that the systemic distribution and the rate of renal excretion of PGs could be altered by high concentrations of PGs, pharmacologically less active PG analogues, some inhibitors of organic acid transport, and by some inhibitors of PG synthesis and PG action.

Animals↗
PubMed2000

Kidney function and sulfate uptake and loss in the freshwater bivalve Toxolasma texasensis.

Toxolasma texasensis acclimated to an artificial pondwater (PW) maintained a concentration of SO4 in the blood of about 1-2 mmol l(-1) . The anion transport inhibitor DIDS (5,5'-diisothiocyanatostilbene 2, 2'-disulfonic acid) reduced the uptake of 35SO4 from the bathing medium by 54%. The clearance of polyethylene glycol (PEG) injected into the blood of T. texasensis ranged between 0.8 and 1.3 ml g(-1) dry tissue h(-1), and provided an estimate of renal filtration in PW-acclimated animals. The clearance of radioactive 35SO4 simultaneously injected into the same animal was about 16% of the PEG clearance, suggesting that sulfate was being reabsorbed by the kidney. Para-aminohippuric acid was cleared about 4.6 times faster than PEG, indicating that this organic acid was subjected to secretion in addition to filtration. When the normal osmotic gradient was abolished by acclimating T. texasensis to 10% seawater (SW), the PEG clearance decreased to 0.17 ml g(-1) dry tissue h(-1). Sulfate clearance in animals acclimated to PW or 10% SW was the same. However, in mussels acclimated to 10% SW, the calculated amount of SO4 reabsorbed was significantly reduced relative to mussels acclimated to PW. T. texasensis conserved SO4 when acclimated to PW, and reduced reabsorption when acclimated to the sulfate-rich 10% SW. When mussels acclimated to 10% SW were returned to PW, there was a transient increase in sulfate clearance during the first 8 h because filtration exceeded reabsorption.

Animals↗
PubMed2001

Effect of feed intake on ovine hindlimb protein metabolism based on thirteen amino acids and arterio-venous techniques.

It has been suggested that protein synthesis in peripheral tissues: (1) responds in a curvilinear manner to increasing feed intake over a wide range of feeding levels; and (2) has a greater sensitivity to intake than protein breakdown. The aim of the present experiment was to test these hypotheses across the ovine hindlimb. Six growing sheep (6-8 months, 30-35 kg), with catheters in the aorta (two), posterior vena cava and jugular vein, received each of four intakes of dried grass pellets (0.5, 1.0, 1.5 and 2.5 x maintenance energy; M) for a minimum of 7 d. A U-13C-labelled algal hydrolysate was infused intravenously for 10 h and from 3-9 h para-aminohippuric acid was infused to measure plasma flow. Arterial and venous plasma were obtained over the last 4 h and the concentrations and enrichments of thirteen (13)C-labelled amino acids (AA) were determined by GC-MS. As intake increased, a positive linear response was found for plasma flow, arterial concentrations of the aromatic and branched-chain AA, total flow of all AA into the hindquarters and net mass balance across the hindquarters (except glycine and alanine). Based on two separate statistical analyses, the data for protein synthesis showed a significant linear effect with intake (except for phenylalanine, glycine and alanine). No significant curvilinear effect was found, which tends not to support hypothesis 1. Nonetheless, protein synthesis was not significantly different between 0.5, 1.0 and 1.5 x M and thus the 2.5 x M intake level was largely responsible for the linear relationship found. There was no significant response in protein breakdown to intake, which supports hypothesis 2.

Amino Acids↗
PubMed1994

[Clinical assessment of 99mTc-MAG3 scintigraphy for impaired renal function].

The renal scintigraphy and clearance of 99mTc-mercaptoacetyltriglycine (MAG3) and 123I-ortho-iodohippuric acid (OIH) were compared in 12 patients with impaired renal function. The patients were first studied with MAG3 and then reinvestigated with OIH two days later. The MAG3 renal scintigraphy gave better quality and functional information in comparison with OIH. The MAG3 and OIH renogram showed identical relative kidney uptake and Tmax, but T1/2 of MAG3 was longer (p < 0.001). The plasma clearance of MAG3 was lower than that of OIH, but they correlated significantly (r = 0.87, p < 0.005). Also, the plasma clearances of MAG3 and para-aminohippuric acid (calculated by the standard clearance technique) showed good correlation (r = 0.77, p < 0.05). The urinary excretion during the first 60 min after injection was the same for the two radiopharmaceuticals. We conclude that 99mTc-MAG3 is a suitable alternative to 123I-OIH in renal scintigraphy.

Adolescent↗
PubMed1986

Functional significance of exaggerated renal thromboxane A2 synthesis induced by cyclosporin A.

Animals and humans undergoing a chronic treatment with cyclosporin A (CyA) show a reduction in glomerular filtration rate (GFR). The cause of this abnormality has not been established. Since CyA interferes with arachidonic acid (AA) metabolism in various cells, we wished to determine whether alterations in renal AA metabolites contribute to deteriorating renal function in rats on CyA. We show that chronic CyA treatment induces a progressive increase in the renal synthesis of thromboxane (TX) A2. This is a selective abnormality in that CyA does not influence the renal synthesis of prostaglandin E2 (PGE2) and prostacyclin (PGI2). A significant negative correlation has been found between TXB2 urinary excretion rate and inulin clearance. No correlation has been observed between TXB2 excretion and p-aminohippuric acid clearance. The withdrawal of CyA is followed by a normalization of both TXB2 urinary excretion rate and GFR. The administration of a selective TXA2 inhibitor, UK-38,485, resulted in a significant reduction in urinary excretion of TXB2 accompanied by a significant increase in GFR. We conclude that chronic treatment with CyA in rats is associated with a selective increase in renal TXA2 synthesis and suggest that this abnormality may play a role in the reduction of GFR.

Animals↗
PubMed1985

Effects of the renal vasodilator prodrug CGP 22 979A and its parent compound CGP 18 137A on renal and central hemodynamics in conscious spontaneously hypertensive rats.

In a previous study we reported that the renal prodrug CGP 22 979A (N-acetyl-L-glutamic acid-N-[N2-(5-n-butyl-2-pyridyl)-hydrazide) causes selective renal vasodilation in conscious spontaneously hypertensive rats (SHR) in doses up to 10 mg/kg. The hydralazine-like parent compound CGP 18 137A (2-hydrazino-5-n-butyl-pyridine) causes general vasodilatation. In the present study we report on renal hemodynamics, excretion of water and sodium and central hemodynamic effects of CGP 18 137A and CGP 22 979A in conscious, unrestrained SHR. CGP 18 137A (1 mg/kg) reduced effective renal plasma flow [measured as plasma clearance of [125I]p-aminohippuric acid] and glomerular filtration rate (measured as plasma-clearance of 51Cr-EDTA), in the first hour after injection. CGP 22 979A (3-30 mg/kg) dose-dependently increased effective renal plasma flow, but not glomerular filtration rate thus reducing filtration fraction. In spite of the lack of increase of glomerular filtration rate, CGP 22 979A increased excretion of sodium and water in a separate group of SHR. CGP 18 137A reduced renal excretory function slightly. In another group of conscious SHR we studied the effects of CGP 18 137A and CGP 22 979A on central hemodynamics. These animals had an electromagnetic flow-probe on the ascending aorta, to measure cardiac output (CO). Mean arterial pressure was measured from a chronic catheter in the abdominal aorta. Total peripheral resistance (TPR) and stroke volume were calculated. CGP 18 137A (0.3-1 mg/kg) reduced mean arterial pressure and TPR whereas CO increased immediately after injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1997

Mechanistic analysis of S-(1,2-dichlorovinyl)-L-cysteine-induced cataractogenesis in vitro.

Chronic exposure to low concentrations of the nephrotoxic cysteine conjugate S-(1,2-dichlorovinyl)-l-cysteine (DCVC) causes cataracts in mice. This study explored mechanisms of DCVC-induced cataractogenesis using explanted lenses from male Sprague-Dawley rats. Lenses placed in organ culture were exposed to 2.5 microM-1 mM DCVC for 24 hr. DCVC caused concentration and time-dependent changes in biochemical markers of toxicity (lenticular adenosine 5'-triphosphate (ATP) content, mitochondrial reduction of the tetrazolium dye MTT, and glutathione (GSH) content) at concentrations >/=25 microM. Lens clarity was adversely affected at concentrations >/=50 microM. Within 24 hr, 1 mM DCVC altered lens ATP content (-77 +/- 2%), mitochondrial MTT reduction (-40 +/- 3%), and GSH content (-19 +/- 4%) (percent difference from controls, p < 0.05). ATP was the most sensitive index of DCVC exposure in this model, while lens weight was not altered. The role of lenticular DCVC metabolism was investigated using the beta-lyase inhibitor aminooxyacetic acid (AOA) and the flavin monooxygenase (FMO) inhibitor methimazole (MAZ). AOA (1 mM) provided nearly complete protection from changes in biochemical parameters and lens transparency caused by DCVC, while MAZ (1 mM) provided only partial protection. The mitochondrial Ca2+ uniport inhibitor ruthenium red (30 microM) and the poly(ADP ribosyl)transferase inhibitor 3-aminobenzamide (3 mM) were only partially protective, whereas adverse changes in lens transparency and biochemical markers were not prevented by an antioxidant (2 mM dithiothreitol) or nontoxic transport substrates (200 microM probenecid or 10 mm phenylalanine, S-benzyl-L-cysteine or para-aminohippuric acid). Calpain inhibitors E64d (100 microM) and calpain inhibitor II (1 mM) were ineffective in preventing opacity formation caused by DCVC. In a small separate study, DCVC toxicity to explanted lenses from cynomologus monkeys was also ameliorated by coincubation with AOA. These results indicate that opacity formation by DCVC in rodent and primate lenses in vitro is primarily mediated via lenticular beta-lyase metabolism of DCVC to a reactive metabolite. Metabolism of DCVC by FMO and perturbations in mitochondrial calcium (Ca2+) homeostasis and increased poly(ADP-ribosylation) of nuclear proteins may play a limited role in opacity formation in vitro. However, opacity formation does not appear to be the result of oxidative stress or calpain activation. DCVC toxicity to the lens was not blocked with competitive inhibitors of the amino acid and organic anion transporters of DCVC as is found in the kidney.

Adenosine Triphosphate↗
PubMed1998

Cancer reduces the metabolic response of muscle to surgical stress in the rat.

The metabolic response to surgical stress is characterized by muscle protein breakdown and mobilization of amino acids, e.g., glutamine, from peripheral tissue to visceral organs. Cancer is related to increased protein breakdown of muscle which may influence the normal metabolic response after surgery. The aim was to study the effects of cancer on postoperative peripheral muscle protein and glutamine turnover. Methylcholanthrene-induced sarcomas were implanted subcutaneously in female Lewis rats. Tumor-bearing rats were studied when the tumor was 5-15% of body weight. Control rats were sham implanted. Hysterectomy was performed in control and tumor-bearing rats as a standardized operative procedure. On the second postoperative day a primed constant infusion of para-aminohippuric acid, l-[2,6-3H]phenylalanine, and l-[3,4-3H]glutamine was given under ether anesthesia. At steady state, hindquarter muscle protein turnover and glutamine kinetics were determined in a three-compartment model. In control rats muscle protein synthesis almost doubled and protein breakdown increased threefold after hysterectomy, with concomitant increased outward amino acid membrane transport rates. Hysterectomy did not change protein synthesis or breakdown rates in tumor-bearing rats. Muscle glutamine production and membrane transport and release increased after hysterectomy in control rats. Tumor-bearing rats had depressed membrane transport rates and showed no surgical stress response related to muscle glutamine metabolism. The present study shows that surgical stress induces an increased mobilization of amino acids, e.g., glutamine, from muscle that does not occur in the cancer-bearing state. The reduced metabolic response to surgery in the cancer-bearing host may be of particular importance for the functioning of visceral organs, which use amino acids like glutamine at a high rate after trauma.

Amino Acids↗
PubMed2002

Isolation, characterization and differential gene expression of multispecific organic anion transporter 2 in mice.

We isolated cDNA encoding a multispecific organic anion transporter 2 (OAT2) from the mouse kidney cDNA library. Isolated mouse OAT2 (mOAT2) consisted of 1623 base pairs that encoded a 540-amino acid residue protein with 12 putative membrane-spanning domains, and the amino acid sequence was 87% identical to that of rat OAT2 (rOAT2). The gene coding for mOAT2, Slc22a7, is found on chromosome 17C. Northern blot analysis revealed that the mOAT2 mRNA is abundantly expressed in the male mouse kidney, whereas it was predominantly expressed in both the liver and kidney of female mice. When expressed in Xenopus laevis oocytes, mOAT2 mediated the high affinity transport of glutarate (K(m) = 15.8 +/- 3.2 microM) and prostaglandin E2 (K(m) = 5.2 +/- 0.5 nM) in a sodium-independent manner. mOAT2-expressing oocytes also mediated the uptake of alpha-ketoglutarate, glutarate, prostaglandin E2, p-aminohippuric acid, methotrexate, ochratoxin A, valproate, and allopurinol. However, we did not observe mOAT2-mediated uptake of salicylate. A wide range of structurally unrelated organic anions inhibited mOAT2-mediated glutarate uptake especially erythromycin, a potent inhibitor. These results indicate that isolated mOAT2 is a multispecific organic anion transporter having some differences in substrate specificity compared with rOAT2. In addition, we found that there exists a sex- and species-related differential gene expression of the OAT2 isoform.

Amino Acid Sequence↗
PubMed1982

Renal tubular transport of folic acid and methotrexate in the monkey.

The renal excretion of folic acid and methotrexate (MTX) was investigated in pentobarbital-anesthetized cynomolgus, rhesus, and AFrican green monkeys by standard clearance and stop-flow techniques. The renal clearance of folic acid was below inulin clearance at all plasma concentrations studied; the (U/P)folic/(U/P)In ratio increased from 0.26 at a concentration of 0.03 mM to a plateau value of 0.9 at concentrations above 0.2 mM, indicating net reabsorption by a saturable system. In stop-flow experiments, base-line (U/P)folic/(U/P)In ratios during free-flow periods were below 1.0, but increased by twofold in stop-flow samples derived from the proximal tubule, indicating net secretion during stopped flow. The stop-flow pattern of MTX excretion was similar, except the base-line flow pattern of MTX excretion was similar, except the base-line (U/P)MTX/(U/P)In ratio exceeded 1.0, indicating net secretion during both free-flow and stopped-flow periods. Secretion of both compounds was inhibited by p-aminohippuric acid and other organic acids but not by L-glutamic acid. It is concluded that folic acid is transported bidirectionally, while evidence was obtained only for secretion of MTX.

Animals↗
PubMed1985

The effects of human atrial 28-amino acid peptide on systemic and renal hemodynamics in anesthetized rats.

The effects of synthetic human atrial 28-amino acid peptide (alpha-human atrial polypeptide) on systemic and renal hemodynamics were examined in two separate groups of Inactin-anesthetized rats. First, mean arterial pressure, heart rate, and cardiac output were measured before and during infusion of the peptide at rates of 0.04-0.67 microgram/kg per min. Cardiac output was determined by the dye-dilution method with a microcuvette inserted into a carotid-femoral arterial shunt. After 10 minutes of infusion, mean arterial pressure, cardiac output, and total peripheral resistance were reduced in a dose-dependent manner by 21% (P less than 0.001), 9% (P less than 0.05), and 11% (P less than 0.05), respectively, with 0.67 microgram/kg per min of alpha-human atrial natriuretic polypeptide. Despite the marked fall in blood pressure, the heart rate did not change. Second, urine volume, urinary sodium excretion, glomerular filtration rate ([3H]inulin clearance) and renal blood flow ([14C]p-aminohippuric acid sodium clearance and hematocrit) were measured. Increases in urine volume, urinary sodium excretion, filtration fraction, and fractional sodium excretion and a decrease in renal vascular resistance were dose dependent: +490% (P less than 0.01), +1340% (P less than 0.01), +19% (P less than 0.05), +1160% (P less than 0.01), and -18% (P less than 0.05), respectively, with 0.67 microgram/kg per min of alpha-human atrial natriuretic polypeptide. The glomerular filtration rate increased with 0.33 and 0.67 microgram/kg per min of alpha-human atrial natriuretic polypeptide (both P less than 0.05), whereas renal blood flow did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗