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PubMed1995

Importance of ornithine transcarbamylase (OTC) deficiency in small intestine for urinary orotic acid excretion: analysis of OTC-deficient spf-ash mice with OTC transgene.

We report the effect of the ornithine transcarbamylase (OTC) transgene composed of 1.3 kb of the 5' flanking region of the rat OTC gene fused to rat OTC cDNA on urinary orotic acid excretion in OTC-deficient spf-ash (sparse-fur with abnormal skin and hair) mice during overnight-starvation and nitrogen loading. During starvation, spf-ash mice with about 6% and 2% of control levels of OTC activity in the liver and small intestine excreted a large amount of orotic acid in the urine. Transgenic spf-ash mice with about 10% and 30% of the control OTC activities in the liver and small intestine did not excrete more than the normal level of orotic acid. Accidental parasitization of transgenic spf-ash mice with ticks (Myocoptes musculinus) resulted in decrease of the OTC activities in the liver and small intestine to the levels in spf-ash mice, and increased excretion of orotic acid. During extermination of the ticks, the mice showed varied levels of OTC activity and orotic acid excretion. On nitrogen loading, transgenic spf-ash mice as well as spf-ash mice excreted larger amounts of orotic acid, while control mice showed no increase in its excretion. The levels of urinary orotic acid were inversely correlated to the logarithms of the OTC activities in the liver and small intestine, the correlation being significantly higher with intestinal OTC than with hepatic OTC activity. These results suggest that the level of OTC activity in the small intestine is important for production of orotic acid.

Animals↗
PubMed2004

Urinary cyclic GMP excretion and blood pressure levels in a general population.

Dysfunction of the nitric oxide (NO) system is potentially involved in the development of hypertension, but only limited data are currently available from experimental or clinical studies. We investigated cross-sectionally the relation between urinary excretion of cyclic guanosine 3',5'-monophosphate (cyclic GMP), a second messenger of NO, and hypertension in a general population sample of Japanese men and women. The samples comprised 1541 subjects (788 men and 753 women) aged 40-79 years who participated in cardiovascular risk surveys between 1997 and 2002 and underwent a 24h urine collection. Urinary excretion of cyclic GMP was measured using a 125I-labeled cyclic GMP radioimmunoassay, and was adjusted for urinary creatinine excretion (nmol/mmol creatinine). Urinary cyclic GMP excretion was 66.0+/-62.0nmol/mmol creatinine (mean+/-S.D.). Compared with normal blood pressure individuals, the multivariate-adjusted mean value of urinary cyclic GMP excretion was significantly higher in people with moderate hypertension, but not higher in severe hypertension. Among subjects with hypertensive end-organ damage, we observed reduced urinary cyclic GMP excretion in severe hypertension and no increased excretion in moderate hypertension, compared with normal blood pressure. Although we had the limited number of subjects with severe hypertension (n=15), our data suggest that NO bioactivity may be increase in the early stage of hypertension but decreased in severe hypertension with end-organ damage.

Adult↗
PubMed2006

Species-, sex-, and age-dependent urinary excretion of cauxin, a mammalian carboxylesterase.

Domestic cats exhibit physiological proteinuria due to the excretion of cauxin, a carboxylesterase, into the urine. In the present report, we demonstrate that cauxin is excreted in a species-, sex-, and age-dependent manner. Although the cauxin gene is conserved in mammals, including human, mouse, and dog, urinary cauxin was found only in member of the genus Felis and lynx (bobcat, and lynx) and not in other Felidae (genus: Panthera and puma) tested. In mature cats, cauxin excretion was higher in intact males than in castrated males or in intact or spayed females. Daily cauxin excretion decreased immediately after castration. Immunohistochemistry confirmed that cauxin expression in the kidney proximal straight tubules was higher in intact males than in castrated males. Urinary cauxin was detectable by Western blotting in cats older than about 3 months, and its excretion increased with age. In a zymographic esterase assay, urine contained a major cauxin band; by contrast, kidney homogenates contained three major bands, comprising two carboxylesterases and an unidentified esterase, and one minor cauxin band. These results suggest that 1. cauxin excretion is regulated by sex hormones, such as testosterone, 2. cauxin functions as an esterase in the urine rather than in kidney cells, and 3. the decomposition products by cauxin are excreted in a species-, sex-, and age-dependent manner, as is cauxin itself.

Aging↗
PubMed2004

Urinary excretion of 8-hydroxydeoxyguanosine and malondialdehyde after high dose radiochemotherapy preceding stem cell transplantation.

The urinary excretion of the hydroxylated DNA base 8-hydroxydeoxyguanosine (8-OHdG) and the lipid peroxidation product malondialdehyde (MDA) was monitored in 11 patients with hematological malignancies undergoing total body irradiation and high-dose chemotherapy preceding bone marrow transplantation. Nine patients showed a prompt increase in urinary 8-OHdG (8-25 times the initial baseline level) on days 0-7 after irradiation onset; the excretion then decreased during the aplastic period and increased again when engraftment took place (in 7 patients). A significant positive correlation was found between urinary 8-OHdG and whole blood leukocyte count, both on day 5 (p =.04, r =.72) and on day 22 (p =.009, r =.80) after irradiation onset. One patient who lacked the first peak of 8-OHdG excretion showed low blood leukocyte counts (less than 2 x 10(9)/l) before therapy onset; this patient, however, later had a successful engraftment and then also showed considerable increases in both 8-OHdG excretion and leukocyte count. These observations suggest leukocytes play a part in the excretion of 8-OHdG after conditioning therapy preceding bone marrow transplantation. As opposed to the biphasic 8-OHdG excretion, the excretion of MDA showed a single peak appearing on days 11-19 after radiochemotherapy onset, i.e., during the period in which the patients suffered from cytopenia, mucositis, and other side effects of the treatment. It is suggested, therefore, that these clinical manifestations are associated with increased lipid peroxidation. Altogether, these findings illustrate the utility of serial urinary samples for monitoring oxidative stress due to conditioning therapy in clinical practice. They also demonstrate that different oxidative stress markers may behave quite differently regarding their appearance in the urine after whole-body oxidative stress.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2004

HSV excretion after bone marrow transplantation: a 4-year survey.

BACKGROUND: Herpes simplex virus (HSV) oral excretions are common after bone marrow transplantation (BMT). OBJECTIVE: We report a 4-year systematic survey of HSV excretions in an adult population who underwent BMT (289 transplantations). STUDY DESIGN: Patients received either intravenous ACV treatment when mucositis occurred or systematic intravenous ACV prophylaxis from initiation of the BMT conditioning until the end of aplasia. All patients were followed up for HSV excretions. RESULTS: Twenty-eight patients (9.7%) excreted HSV. The occurrence of HSV excretions was similar in both allogeneic and autologous transplant patients. The incidence was significantly lower when ACV was systematically used after transplantation (2.5%) compared to when ACV was implemented for mucositis (12%). ACV-resistant HSV was detected in three patients who received allogeneic transplantation, representing 27% of allogeneic recipients excreting HSV. CONCLUSION: HSV infection prophylaxis with high dose of intravenous ACV resulted in a decreased incidence of HSV excretion. Nevertheless, the risk of emergence of ACV resistance, especially among allogeneic transplant patients, appears to be identical whatever the route and dose of ACV prophylaxis.

Acyclovir↗
PubMed2004

Depression and anxiety symptoms are related to increased 24-hour urinary norepinephrine excretion among healthy middle-aged women.

OBJECTIVE: Depression is a risk factor for morbidity and mortality in a variety of populations, and anxiety has also been associated with risk of mortality among cardiac patients. Dysfunction of the autonomic nervous system may be involved in this risk. The primary goal of this study was to evaluate the relationship between levels of self-reported symptoms of depression and anxiety and 24-hour urinary catecholamine excretion. METHOD: Ninety-one women aged 47-55 years were evaluated. Depression symptoms were assessed with the Beck Depression Inventory (BDI) and state anxiety was assessed with the state anxiety portion (SAI) of the Spielberger State-Trait Anxiety Inventory (STAI). Twenty-four hour urine collections were assayed for epinephrine (EPI), norepinephrine (NE) and cortisol (CORT). EPI, NE and CORT were indexed by body surface area to control for individual differences in body size. RESULTS: Higher levels of depression symptoms were associated with increased 24-hour NE excretion (r=.27, P=.009), with depressed women (n=17, BDI scores >/=10) exhibiting an approximately 25% higher rate of urinary NE excretion than women with BDI scores <10 (n=74), P=.007. Higher levels of state anxiety were also related to greater NE excretion (r=.28, P=.01), and CORT excretion was related to both depression (r=.23, P=.02) and anxiety (r=.22, P=.04). Depression and anxiety symptoms were unrelated to urinary EPI excretion. CONCLUSIONS: The current findings that higher levels of depression and anxiety symptoms are related to increased 24-hour urinary NE and CORT excretion among women suggests that depression and anxiety may be associated with increased sympathetic nervous system (SNS) activity, and are consistent with the possibility that SNS activity may play a role in the increased mortality associated with depression in community-dwelling older adults.

Anxiety↗
PubMed2005

Zea mays L. extracts modify glomerular function and potassium urinary excretion in conscious rats.

Diuretic and uricosuric properties have traditionally been attributed to corn silk, stigma/style of Zea mays L. Although the diuretic effect was confirmed, studies of the plant's effects on renal function or solute excretion were lacking. Thus, we studied the effects of corn silk aqueous extract on the urinary excretion of water, Na+, K+, and uric acid. Glomerular and proximal tubular function and Na+ tubular handling were also studied. Conscious, unrestrained adult male rats were housed in individual metabolic cages (IMC) with continuous urine collection for 5 and 3 h, following two protocols. The effects of 25, 50, 200, 350, and 500 mg/kg body wt. corn silk extract on urine volume plus Na+ and K+ excretions were studied in water-loaded conscious rats (2.5 ml/100 g body wt.) in the IMC for 5 h (Protocol 1). Kaliuresis was observed with doses of 350 (100.42 +/- 22.32-120.28 +/- 19.70 microEq/5 h/100 g body wt.; n = 13) and 500 mg/kg body wt. (94.97+/- 29.30-134.32 +/- 39.98 microEq/5h/100 g body wt.; n = 12; p<0.01), and the latter dose resulted in diuresis as well (1.98 +/- 0.44-2.41 +/- 0.41 ml/5 h/100 g body wt.; n = 12; p<0.05). The effects of a 500 mg/kg body wt. dose of corn silk extract on urine volume, Na+, K+ and uric acid excretions, and glomerular and proximal tubular function, were measured respectively by creatinine (Cler) and Li+ (ClLi) clearances and Na+ tubular handling, in water-loaded rats (5 ml/100 g body wt.) in the IMC for 3 h (Protocol 2). Clcr (294.6 +/- 73.2, n = 12, to 241.7 +/- 48.0 microl/ min/100 g body wt.; n = 13; p<0.05) and the Na+ filtered load (41.9 +/- 10.3, n = 12, to 34.3 +/- .8, n = 13, p<0.05) decreased and ClLi and Na+ excretion were unchanged, while K+ excretion (0.1044 +/- 0.0458, n=12, to 0.2289 +/- 0.0583 microEq/min/100 body wt.; n = 13; p<0.001) increased. For Na+ tubular handling, the fractional proximal tubular reabsorption (91.5 +/- 3.5, n = 12, to 87.5 +/- 3.4%; n = 13; p<0.01) decreased, and both fractional distal reabsorptions--I and II--increased (96.5 +/- 1.5, n = 12, to 97.8 +/- 0.9%; n = 13; p<0.01; and 8.2 +/- 3.5, n = 12, to 12.2 +/- 3.4%, n = 13, p<0.01, respectively). To summarize, in water-loaded conscious rats (2.5 ml/100 body wt.), corn silk aqueous extract is diuretic at a dose of 500 mg/kg body wt. and kaliuretic at doses of 350 and 500 mg/kg body wt. In water-loaded conscious rats (5.0 ml/100 g body wt.), corn silk aqueous extract is kaliuretic at a dose of 500 mg/kg body wt., but glomerular filtration and filtered load decrease without affecting proximal tubular function, Na+, or uric acid excretion.

Animals↗
PubMed2001

Effects of kaliuretic peptide on sodium and water excretion in persons with congestive heart failure.

Kaliuretic peptide, a 20-amino acid peptide hormone synthesized in the heart, enhances urine flow twofold, whereas atrial natriuretic peptide (ANP) enhances urine flow four- to 11-fold in healthy persons. The present investigation was designed to (1) determine whether kaliuretic peptide may have beneficial diuretic effects in persons with congestive heart failure (CHF), and (2) compare its beneficial effects with ANP in the treatment of CHF. Kaliuretic peptide (100 ng/kg body weight/min) given intravenously for 60 minutes to subjects with New York Heart Association class III CHF increased urine flow fourfold (p <0.001), which was maximal 212 hours after its infusion was stopped. Kaliuretic peptide enhanced sodium excretion threefold in subjects with CHF (p <0.01). Kaliuretic peptide increased the urinary excretion rate of potassium ion and fractional excretion of potassium 3.5- and twofold (p <0.05), respectively. ANP (same concentration) did not significantly enhance urine flow. ANP enhanced sodium excretion two- to sixfold in half of the CHF subjects, whereas it had no effect on sodium excretion in the other half. ANP did not significantly increase fractional excretion of sodium but did increase fractional excretion of potassium (p <0.05) during the first 20 minutes of its infusion. ANP-infused patients with CHF became hypotensive. None became hypotensive secondary to kaliuretic peptide. These data indicate that the diuretic properties of kaliuretic peptide in persons with CHF, as opposed to those of ANP, are not diminished (but rather are increased) compared with their effects in healthy persons. In patients with CHF, kaliuretic peptide causes a natriuresis-a feature not observed in those without sodium retention.

Adult↗
PubMed1994

Normal values of urinary albumin and total protein excretion during pregnancy.

OBJECTIVE: Our purpose was to determine the normal 24-hour excretion values of urinary albumin and total protein in healthy pregnant women. STUDY DESIGN: We evaluated 270 healthy pregnant women < or = 35 years old without a history of diabetes, hypertension, pyelonephritis, preeclampsia, or renal or connective tissue disease. Adequacy of 24-hour collection was determined by creatinine excretion. RESULTS: The mean protein excretion in 24 hours was 116.9 mg, upper 95% confidence limit 259.4 mg. The mean albumin excretion in 24 hours was 11.8 mg, upper 95% confidence limit 28.7 mg. Both protein and albumin excretion increased after 20 weeks of gestation. No patient had evidence of microalbuminuria, defined as urinary albumin excretion > 30 mg/L. CONCLUSION: These data support 260 mg per 24 hours of urinary protein and 29 mg per 24 hours of albumin as the upper limit of normal in pregnancy. Albumin accounts for a small fraction of total urinary protein excretion.

Adult↗
PubMed1983

Antibiotic excretion into the bile after hepatic-portojejunostomy in biliary atresia.

Antibiotic excretion into the bile was studied using LMOX and CMZ in 16 postoperative cases of biliary atresia patients who had had hepatic portoenterostomy with Suruga II type enterostomy with the following results: Group I: Excellent excretion which was almost the same as that seen with adult patients; Group IIa: Good or poor excretion, depending on the amount of bile flow and liver function; Group IIb: Very poor excretion; Group III: Good excretion but depending on the amount of bile flow and liver function. As the total bile acid level in bile showed a higher level, the biliary excretion of antibiotics was greater. Our study indicates that antibiotic excretion into the bile in infants is closely related to the condition of the liver function and the biliary passages.

Bile↗
PubMed1975

Free catecholamine excretion in the urine in normal infants and in those with marasmus or kwashiorkor.

Free catecholamine (epinephrine + norepinephrine) excretions of normal male infants 2.1-3.2, 4.5-10.6, and 12.5-18.5 months of age, respectively, and of infants and children with marasmus or marasmic kwashiorkor were measured on three consecutive days after admission and after partial rehabilitation. In normal infants, particularly the older ones, the first day's excretion was higher than that of the next two days, probably in response to the stress of the procedures. There was an increase with age, but on a surface area basis, the differences were not significant, the three age groups excreting 15.1 plus or minus 10.2, 23.8 plus or minus 20.9, and 24.7 plus or minus 14.3 mug/m-2/day, respectively. Excretions of marasmic infants on admission were not significantly different from those of the control children. Higher mean values were due to elevated excretions of infants with severe infection. After partial rehabilitation, excretions were similar to those of control subjects. In children with marasmic kwashiorkor excretions were no different from those of control infants, except in severely infected children. Admission values revealed more day-to-day variation than recovery values or than those of normal and marasmic infants, in whom subject to subject variation was more marked.

Adaptation, Physiological↗
PubMed1985

Renal excretion of calcium and phosphate in preterm and term infants.

We studied urinary phosphate and calcium excretion in preterm and term infants during the first 3 months of life. The infants were mainly breast-fed, and the average phosphate intake ranged between 0.5 and 1 mmol/kg/day. During the first week of life urinary phosphate excretion was significantly higher in preterm than in term infants, whereas parathyroid hormone values were the same. After the first week of life urinary phosphate and calcium excretion were the same in preterm and term infants. Fractional excretion of phosphate was low (range 1% to 6%). In both groups calcium excretion was low during the first weeks of life, and increased thereafter to 5 and 3 mmol/1.73 m2/day, respectively. The urinary calcium/creatine ratio generally exceeded 2.0 (mmol/mmol) in preterm infants after the second week of life. These results are compatible with a state of relative phosphate deficiency, resulting in an adaptively low urinary phosphate excretion and an inability to form bone minerals, and therefore relatively high urinary calcium excretion.

Calcium↗
PubMed1989

Substrate disposal in metabolic disease: a comparison between rates of in vivo propionate oxidation and urinary metabolite excretion in children with methylmalonic acidemia.

The relative importance of endogenous metabolism and urinary metabolite excretion was assessed in vivo in six children with methylmalonic acidemia by examining the kinetics of the immediate precursor to methylmalonate, propionate. Total production and oxidation of propionate were measured by means of a continuous infusion of (1-13C)propionate and were compared with the urinary excretion of propionate metabolites. Propionate oxidation was substantial (mean 48.9 mumol/kg/hr +/- SD 18.0) and, in four children, exceeded urinary metabolite excretion (mean urinary excretion in all subjects 40 mumol/kg/hr +/- 25). The sum of urinary excretion and oxidation rates (88 mumol/kg/hr +/- 29) approximated the total propionate production (93.4 +/- 37.0), suggesting that these routes together constitute the major mechanisms of propionate disposal. These results suggest that propionate oxidation is an important route of disposal in methylmalonic acidemia. Variations in the relative proportions of propionate disposal through oxidation and urinary excretion may be one reason for the often poor correlation between clinical status and urinary metabolite excretion. Measurement of urinary metabolite concentration alone may not always reflect clinical status and responses to treatment accurately.

Humans↗
PubMed1989

Uric acid excretion in children with urolithiasis.

Urinary uric acid excretion was assessed in 38 children to determine whether hyperuricuria was a risk factor in children with urolithiasis. Uric acid excretion (measured per deciliter glomerular filtration rate), and fractional excretion of uric acid were similar in 27 children with hypercalciuria and calcium oxalate urinary stones, in six children with idiopathic calcium oxalate urolithiasis, and in five with uric acid urolithiasis, of whom four were white boys and one was an Asian girl. One boy with a urate stone had cystinosis. Serum uric acid concentrations exceeded 6.0 mg/dl (360 mumol/L) in two children with hypercalciuria and in two patients with idiopathic calcium oxalate urolithiasis. None of the children with calcium urolithiasis had excessive urinary excretion of uric acid. In children with hypercalciuria, uric acid excretion did not change significantly when dietary sodium was increased from 1.0 to 5.0 gm/1.73 m2. We conclude that excessive urinary uric acid excretion is seldom an additional risk factor in children with calcium urolithiasis and that dietary sodium chloride does not have a strong influence on urinary excretion of uric acid in children with hypercalciuria.

Adolescent↗
PubMed2006

Desmopressin resistant nocturnal polyuria secondary to increased nocturnal osmotic excretion.

PURPOSE: We investigated the role of increased solute excretion in children with desmopressin resistant nocturnal enuresis and nocturnal polyuria. MATERIALS AND METHODS: A total of 42 children with monosymptomatic nocturnal enuresis and significant nocturnal polyuria with high nocturnal urinary osmolality (more than 850 mmol/l) were not responding to desmopressin. A 24-hour urinary concentration profile was obtained with measurement of urine volume, osmolality, osmotic excretion and creatinine. The control group consisted of 100 children without enuresis. RESULTS: Based on osmotic excretion patients were classified into 3 groups. Group 1 had 24-hour increased osmotic excretion, most likely secondary to a high renal osmotic load. This was probably diet related since 11 of these 12 patients were obese. Group 2 had increased osmotic excretion in the evening and night, probably due to a high renal osmotic load caused by the diet characteristics of the evening meal. Group 3 had deficient osmotic excretion during the day, secondary to extremely low fluid intake to compensate for small bladder capacity. CONCLUSIONS: Nocturnal polyuria with high urinary osmolality in our patients with desmopressin resistant monosymptomatic nocturnal enuresis is related to abnormal increased osmotic excretion. This may be explained by their fluid and diet habits, eg daytime fluid restriction, and high protein and salt intake.

Adolescent↗
PubMed1999

Cyclic guanosylmonophosphate urinary excretion in parasympathicomimetic or parasympatholytic syndromes induced by reserpine or diphemanil-methylsulfate.

Parasympathetic hyperactivity is found in some infants presenting faint episodes and could be responsible of certain Sudden Infant Death Syndrome cases. Therefore it was interesting to look for a noninvasive biochemical indicator of parasympathetic activity. A parasympaticomimetic syndrome associated with muscarinic receptor stimulation, which has been followed during 48 h, was obtained in the awake rat by reserpine injection (6.25 mg/kg at T0 and T24h), and a model of prolonged parasympatholytic syndrome, by administration of diphemanil-methylsulfate (DPMS), a muscarinic receptor inhibitor, in drinking water (mean daily dosis: 150 mg/kg). Significant bradycardia and tachycardia were respectively observed. In the reserpine-treated rats we found significantly increased cyclic guanosylmonophosphate (cGMP) urinary excretion between T24h and T48h, when compared with vehicle-treated controls (+87% in one experiment, +135% in the other, when expressed in pmol/microg creatinine); norepinephrine urinary excretion between T24h and T48h was decreased (-44%); the increase in cGMP urinary excretion was not significantly modified by the NO-synthase inhibitor, L-nitroarginine-methyl-ester. In the DPMS-treated rats, we observed a significantly decreased cGMP (-20%) and increased norepinephrine urinary excretion (+61%). Thus cGMP excretion varied in opposite directions in the reserpine- and DPMS-treated rats. The link between these modifications in cGMP excretion and muscarinic receptor stimulation or blockade has still to be fully demonstrated. Urinary cGMP excretion could be tested as screening parameter in infants at risk of faint episodes associated with bradycardia.

Animals↗
PubMed1999

Biliary cholesterol and bile acid excretion do not increase in hamsters fed cereal-based diets containing cholesterol.

The major compensatory responses to increased cholesterol consumption are decreased cholesterol synthesis and increased cholesterol excretion through the bile either as free cholesterol or bile acids. The objective of this study was to test the hypothesis that biliary cholesterol excretion is increased in hamsters fed low levels of cholesterol reflecting normal human intake. The hypothesis was based on observations that hamsters generally resist changes in bile acid synthesis when fed large amounts of cholesterol; therefore, increased biliary cholesterol excretion represents a potentially significant pathway for elimination of excess cholesterol in this species. Hamsters were fed modified NIH-07 cereal-based diets containing 0.02%, 0.03%, and 0.05% cholesterol (0.04, 0.06, and 0.10 mg cholesterol/kcal, respectively). The primary response to increasing amounts of dietary cholesterol was downregulation of whole-body cholesterol synthesis, reduced from 3.93+/-0.14 micromol x d(-1) x 100 g(-1) body weight in hamsters fed 0.02% cholesterol to 0.52+/-0.14 micromol x d(-1) x 100 g(-1) in the 0.05% cholesterol group. Biliary cholesterol excretion was also slightly reduced in hamsters fed 0.05% cholesterol, whereas bile acid excretion was not altered by dietary cholesterol. Despite a pronounced downregulation of whole-body cholesterol synthesis, liver and plasma cholesterol concentrations increased in hamsters fed 0.05% cholesterol. The data indicate that increased biliary cholesterol excretion is not a major compensatory route of cholesterol excretion in hamsters consuming cholesterol. Furthermore, cholesterol added to the diet at 0.05% appears to be the approximate threshold at which compensatory mechanisms can prevent increases in liver and plasma cholesterol in male Syrian hamsters. Consequently, this species may be an appropriate animal model for "hyperresponding" individuals in the human population.

Animals↗
PubMed1999

Effect of organic anions and bile acid conjugates on biliary excretion of taurine-conjugated bile acid sulfates in the rat.

Biliary organic anion excretion is mediated by an ATP-dependent primary active transporter, canalicular multispecific organic anion transporter/multidrug resistance protein 2. On the other hand, a multiplicity of canalicular organic anion transporter/multidrug resistance protein 2 has been suggested. Therefore, to examine the effect of hydrophobicity on the substrate specificity of canalicular multispecific organic anion transporter/multidrug resistance protein 2, we examined the effect of organic anions and bile acid conjugates on biliary excretion of three taurine-conjugated bile acid sulfates with different hydrophobicity, taurolithocholate-3-sulfate, taurochenodeoxycholate3-sulfate, and taurocholate-3-sulfate in rats. Biliary excretions of these bile acid conjugates were delayed in Eisai hyperbilirubinemic rats. Biliary excretion of these bile acid conjugates was inhibited by sulfobromophthalein, whereas biliary excretion and taurocholate-3-sulfate was not inhibited by phenolphthalein glucuronide. Taurolithocholate-3-sulfate and ursodeoxycholate-3-glucuronide decreased biliary excretion of taurochenodeoxycholate-3-sulfate and taurocholate-3-sulfate, but ursodeoxycholate-3,7-disulfate did not affect biliary excretion of taurochenodeoxycholate-3-sulfate and taurocholate-3-sulfate. These findings indicate that very hydrophilic organic anions are not good substrates of canalicular multispecific organic anion transporter/multidrug resistance protein 2.

Animals↗