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PubMed1997

Effect of amrinone on portal hemodynamics and tissue blood flow in the isolated perfused rat liver.

We studied the effect of amrinone on portal perfusion pressure, perfusion flow, and tissue blood flow using an isolated perfused rat liver model. In the constant perfusion flow model, amrinone effectively decreased perfusion pressure in the precontracted state by adenosine triphosphate (ATP) or norepinephrine. Amrinone dose-dependently decreased portal perfusion pressure increased by calcium chloride. Similarly, amrinone dose-dependently increased portal perfusion flow decreased by ATP in the constant perfusion pressure model. Amrinone effectively increased tissue blood flow decreased by ATP or norepinephrine measured by laser-Doppler flowmetry. A specific inhibitor of the biosynthesis of nitric oxide, N omega-nitro-L-arginine, did not affect the hemodynamic effect of amrinone, suggesting that nitric oxide is not involved in the portal vasodilating effect of amrinone. We conclude that amrinone increases portal blood flow by decreasing perfusion pressure and contributes to increasing tissue blood flow of the liver without the involvement of nitric oxide.

Amrinone↗
PubMed1997

Reactivity of the isolated perfused rat tail vascular bed.

Isolated segments of the perfused rat tail artery display a high basal tone when compared to other isolated arteries such as the mesenteric and are suitable for the assay of vasopressor agents. However, the perfusion of this artery in the entire tail has not yet been used for functional studies. The main purpose of the present study was to identify some aspects of the vascular reactivity of the rat tail vascular bed and validate this method to measure vascular reactivity. The tail severed from the body was perfused with Krebs solution containing different Ca2+ concentrations at different flow rates. Rats were anesthetized with sodium pentobarbital (65 mg/kg) and heparinized (500 U). The tail artery was dissected near the tail insertion, cannulated and perfused with Krebs solution plus 30 microM EDTA at 36 degrees C and 2.5 ml/min and the procedures were started after equilibration of the perfusion pressure. In the first group a dose-response curve to phenylephrine (PE) (0.5, 1, 2 and 5 micrograms, bolus injection) was obtained at different flow rates (1.5, 2.5 and 3.5 ml/min). The mean perfusion pressure increased with flow as well as PE vasopressor responses. In a second group the flow was changed (1.5, 2, 2.5, 3 and 3.5 ml/min) at different Ca2+ concentrations (0.62, 1.25, 2.5 and 3.75 mM) in the Krebs solution. Increasing Ca2+ concentrations did not alter the flow-pressure relationship. In the third group a similar protocol was performed but the rat tail vascular bed was perfused with Krebs solution containing PE (0.1 microgram/ml). There was an enhancement of the effect of PE with increasing external Ca2+ and flow. PE vasopressor responses increased after endothelial damage with air and CHAPS, suggesting an endothelial modulation of the tone of the rat tail vascular bed. These experiments validate the perfusion of the rat tail vascular bed as a method to investigate vascular reactivity.

Animals↗
PubMed1989

Effects of 3-hydroxybutyrate and hyperosmolarity on glucagon release from isolated perfused canine pancreas.

The effects of 3-hydroxybutyrate (3-OHB) and hyperosmolarity on glucagon secretion were examined in the isolated perfused canine pancreas. When 3-OHB was infused for 15 min into the pancreas perfused with 2.8 mM glucose, 5 and 20 mM sodium 3-OHB inhibited it after a transient stimulation, whereas a similar transient stimulation was observed also by the infusion of 20 mM NaCl in a control experiment. The above inhibition was not observed under the perfusate condition of 5.5 mM glucose plus 10 mM arginine. When the isolated canine pancreas was perfused under the perfusate condition of acidosis (pH 7.1), ketoacidosis (pH 7.1 and 20 mM 3-OHB) or hyperosmolarity (+60 mOsm/kg with sucrose) throughout the experiment, the glucagon concentrations produced by 2.8 mM glucose under the ketoacidotic and hyperosmolar conditions, were less than half of those obtained under the standard condition. The insulin level was not influenced by the above perfusate conditions. These results suggest that 3-OHB inhibits glucagon secretion stimulated by glucopenia, but does not inhibit it stimulated by amino acids, and that hyperosmolarity inhibits glucagon secretion but does not inhibit insulin secretion. The pathophysiological significance of these results must be slight, considering the presence of hyperglucagonemia during prolonged starvation or diabetic ketoacidosis.

3-Hydroxybutyric Acid↗
PubMedDate not supplied

Effect of ischemia-reperfusion on the post-rest inotropy of isolated perfused rat heart.

UNLABELLED: This paper aims to study the effect of ischemia-reperfusion on the post-rest inotropy and to characterize post-rest B1:B2 ratio as an index of intracellular Ca(2+) overload. When the rest interval between the cardiac beats is increased, the magnitude of the post-rest beats is increased. First beat (B1) is maximally potentiated with exponential decline of the second (B2) and subsequent beats, thereby establishing a normal B1:B2 ratio of post- rest inotropy of the cardiac muscle. The rest potentiation of B1 and subsequent decay in the magnitude B2 is thought to develop from the time-dependent changes in the Ca(2+)-uptake and release from the sarcoplasmic reticulum (SR). Ca(2+)-kinetics of SR can be modulated by a variety of interventions which produce Ca(2+) loading of the SR. METHODS: Isolated perfused (K-H buffer, 34 degrees C) rat hearts were paced at 1 Hz (steady state frequency). Interbeat intervals between 1s and 10s were introduced and the recovery in the left ventricular contractile force (Pmax) of post-rest B1 and B2 for each interval was recorded. Their relative relationship was computed and compared under control and experimental conditions. RESULTS: High extracellular Ca(2+) (2.50 to 7.0 mM) or low extracellular Na(+) (50% of control), and ischemia (60 min, 34 degrees C) - reperfusion (30 min, 34 degrees C) caused the reversal of the control relationship of the B1 to B2, with B2 being more potentiated than B1, accompanied by the appearance of after-contractions during the rest intervals of 4s or more. The mean (+/- SE) control B1:B2 ratio (at 4s interval) of 1.12 +/- 0.05 was significantly (P<0.001) reduced to 0.93 +/- 0.07; 0.89 +/- 0.01; and 0.96 +/- 0.02 after high Ca(2+) (6 mM) perfusion, low Na(+)(50%) perfusion and ischemia-reperfusion respectively. Simultaneous perfusion with ryanodine (1 microM) abolished the after-contractions and significantly increased the reduced ratios. The time course of changes in B1:B2 ratio after graded ischemia-reperfusion showed a significant fall in the ratio between 30 and 60 min of ischemia. A parallel change in Pmax and a significant rise in the left ventricular end-diastolic pressure, indicating an irreversible phase of the injury was recorded. No significant changes in B1:B2 ratio were detected during the reversible phase (<30 min) of the ischemia-reperfusion injury. CONCLUSIONS: Ischemia-reperfusion induces significant alterations in the relative ratio of the post-rest contractions of the left ventricle in isolated perfused rat heart. The altered ratios were characterized to predict the irreversibility of the reperfusion injury and to index the extent of Ca(2+)-loading of the sarcoplasmic reticulum.

Animals↗
PubMed1995

Effect of S-adenosyl-L-methionine on ethanol cholestasis and hepatotoxicity in isolated perfused rat liver.

We investigated whether S-adenosyl-L-methionine (SAMe) influences the inhibitory effect of ethanol on bile secretion and ethanol hepatotoxicity in the isolated perfused rat liver. SAMe (25 mg/kg intramuscularly three times a day) was administered for three days consecutively. Liver was then isolated and perfused with taurocholate to stabilize bile secretion and exposed to 1% ethanol for 70 min. The effect of ethanol on bile flow, bile salt biliary secretion, oxygen liver consumption, AST and LDH release in the perfusate, and hepatic concentration of glutathione, malondialdehyde, and diene conjugates was compared between SAMe-treated livers (N = 11) and paired controls (N = 11). Control experiments without ethanol were also performed (N = 6). Exposure to 1% ethanol induced a significantly (P < 0.03) higher inhibition of bile flow (-35% vs 17%) and bile salt secretion (-28% vs 16%) in untreated compared with SAMe-treated livers. During 1% ethanol exposure, the release of LDH and AST in the perfusate was significantly lower (P < 0.02) in SAMe-treated livers. Oxygen liver consumption was markedly inhibited by 1% ethanol administration (P < 0.02 vs controls without ethanol), an effect almost totally prevented by SAMe treatment (P < 0.02 vs ethanol controls). The hepatic concentration of total glutathione was significantly (P < 0.02) decreased by 1% ethanol exposure, but this effect was less pronounced in SAMe-treated than in untreated controls (P < 0.02). The hepatic levels of malondialdehyde and diene conjugates were not significantly changed by ethanol exposure in either SAMe-treated or control livers in comparison to ethanol-free controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Metabolism and cytotoxicity of naphthalene oxide in the isolated perfused mouse lung.

Naphthalene produces selective injury to Clara cells in the mouse in vivo and in the isolated perfused lung. To investigate the role of circulating reactive metabolites in lung injury, the stability, metabolism and cytotoxicity of naphthalene oxide, a reactive intermediate, were examined in the perfused mouse lung. The T1/2 of naphthalene oxide is 4 min in Waymouth's medium. Addition of 5% bovine serum albumin to the medium increased the half-life of the epoxide to 11 min. Perfusion of the lung with 0.2 or 2 mumol of naphthalene oxide decreased pulmonary reduced glutathione levels to 62 and 42% of control, respectively. 1,4-Naphthoquinone and naphthol-glucuronide represented 36 and 25% of the total polar metabolites isolated after infusion of naphthalene oxide, whereas dihydrodiol and thioether conjugates were minor metabolites. In comparison, thioethers and dihydrodiol were the primary metabolites isolated from lungs perfused with [14C]naphthalene. Histologic examination of the lungs fixed 4 hr after infusion of naphthalene oxide (0.25-1.0 mumol/60 min) revealed selective vacuolation and necrosis of Clara cells, significant decreases in the mass of bronchiolar Clara cells and increases in the mass of vacuolated cells. Injury to lungs perfused with naphthalene or secondary metabolites such as naphthoquinones, 1-naphthol and 1,2-dihydro-1,2-dihydroxynaphthalene was less dramatic. In contrast to other studies implicating quinones as mediators of aromatic hydrocarbon toxicity, the current work suggests that epoxides play a significant role in naphthalene-induced lung injury. This investigation also demonstrates that circulating epoxides are capable of eliciting selective Clara cell injury.

Animals↗
PubMed1986

Na+-dependent p-aminohippurate transport at the basolateral side of the isolated perfused rat kidney.

The uptake of p-amino[3H]hippurate by isolated perfused rat kidney was studied to characterize the mechanism which was responsible for organic anion transport process. A rapid injection multiple indicator dilution technique and the distributed two-compartment model of Sawada et al. (Computer Methods Programs Biomed., 20 (1985) 51) were employed. Some characteristics of a carrier-mediated transport from the antiluminal space to the intracellular space for p-aminohippurate at the basolateral side were demonstrated: the uptake was stimulated by the countertransport effect and showed Na+ dependency. These findings are consistent with p-amino[3H]hippurate's being taken up into the isolated rat basolateral membrane vesicle by Na+-dependent carrier-mediated transport (J. Pharmacol. Exp. Ther. 227 (1983) 122). It is suggested that the multiple indicator dilution technique is a sensitive new method to study the mechanisms of renal tubular transport in the living kidney as an organ.

Aminohippuric Acids↗
PubMed1993

Physiological pharmacokinetics of solutes in the isolated perfused rat hindlimb: characterization of the physiology with changing perfusate flow, protein content, and temperature using statistical moment analysis.

Distribution of Evans Blue (EB), sucrose, and water into the isolated perfused rat hindlimb was studied under various conditions using the multiple indicator dilution (MID) technique. Statistical moment analysis of the outflow profiles for the EB, sucrose, and water were used to define the vascular, extravascular, and total water spaces, respectively. The varied perfusion conditions included albumin content (2, 4.7, and 7%), temperature (25, 37, and 42 C), perfusate flow rate (2, 4, 8, and 12 ml/min) and the presence/absence of red blood cells. The range of studies undertaken were chosen to represent the variety of conditions used in the preparation of both isolated animal and human limbs, the latter being particularly important in cytotoxic therapy for recurrent malignant melanoma. The distribution volumes of EB, sucrose, and water were dependent on the flow rate and the albumin content of perfusate. The normalized variances (CV2) of the markers were of the following order: sucrose (2.18) > water (1.58) > EB (0.68), indicating that some disequilibrium occurs during the capillary exchange of water and sucrose. It is suggested that a Krebs-Henseleit buffer containing 2% BSA is a suitable perfusate for most studies of the isolated rat hindlimb perfusion. The effect of albumin concentration manifests itself only at higher flows.

Animals↗
PubMed1997

Postnatal development of vascular resistance of the rabbit isolated perfused kidney: modulation by nitric oxide and angiotensin II.

Studies were performed on isolated perfused kidneys (IPK) from postnatal developing rabbits to ask 1) whether the high renal vascular resistance (RVR) at birth involves intrinsic renal mechanisms, 2) whether nitric oxide (NO) release is involved in the modulation of renal vascular tone, and 3) whether NO modulates exogenous angiotensin II (AII)-induced vasoconstrictions. Kidneys isolated from 1-wk-old (during nephrogenesis), 3-wk-old (after nephrogenesis), and 6-wk-old rabbits were perfused in the presence of 10(-5) M indomethacin. RVR decreased with age from 12.7 +/- 0.6 at 1 wk to 10.1 +/- 0.5 mm Hg min g mL-1 at 6 wk. N omega-Nitro-L-arginine methyl ester (L-NAME, 10(-4) M) comparably increased RVR by about 30% at 1, 3, and 6 wk. The vasoconstrictions induced by 10(-8) M AII increased basal pressure from 28% at 1 wk to 78% at 6 wk and were potentiated by L-NAME by about 100%. In contrast, the vasoconstrictions induced by 10(-10) M AII decreased from 8% at 1 wk to 0% at 6 wk and were potentiated by L-NAME by about 250% at 1 and 3 wk. We conclude that during postnatal development: 1) RVR in IPK decreases in absence of AII and extrarenal influences, suggesting that high RVR at birth involves intrinsic mechanisms, 2) L-Arg/NO modulates basal tonus in developing IPK, and, 3) renal vasoconstrictor responses to exogenous AII are buffered by NO at early postnatal stages and follow an AII concentration-dependent developmental pattern. A specific neonatal high affinity AII/NO interaction disappearing after nephrogenesis completion precedes a low affinity AII/NO interaction, which progressively increases toward adult ages. These findings are in favor of a specific involvement of AII-NO interactions in the control of developing renal hemodynamics.

Age Factors↗
PubMed1992

Influence of angiotensin II-induced alterations in renal flow on excretion of cefonicid in isolated perfused rat kidneys.

The effects of variations in renal perfusate flow on the excretion of cefonicid was examined in isolated perfused rat kidneys. Cefonicid, an expanded-spectrum cephalosporin, is primarily eliminated by active tubular secretion and is neither metabolized nor reabsorbed in the isolated kidney. We used angiotensin II (AII), a strong vasoconstrictor hormone of the afferent and the efferent arterioles in the kidney, to determine whether the renal and secretion clearances, as well as the excretion ratio (ER = CLR/[fu x GFR], where CLR is renal clearance, fu is the unbound fraction, and GFR is glomerular filtration rate), of this low-extraction compound can be altered by a decreased perfusion flow. Control studies were performed in the absence (n = 5) and presence (n = 4) of AII; cefonicid studies were performed in the absence (n = 4) and presence (n = 5) of AII. AII (1 to 4 ng/min) and cefonicid (5 to 10 micrograms/min) were infused into the perfusate. Cefonicid was assayed by high-performance liquid chromatography, and its protein binding was determined by ultrafiltration. AII decreased the perfusate flow rate and increased the renal vascular resistance and filtration fraction of the isolated kidney in the presence and absence of cefonicid. The glomerular filtration rate remained unchanged among the groups. The fractional excretion of glucose was low and steady, indicating a well-preserved tubular function. Although the unbound fraction was unchanged between treatments, the renal and secretion clearances and the excretion ratio of cefonicid were reduced by about 40% in the presence of AII (excretion ratios, 10.3 without AII versus 6.03 with AII). These results suggest that the altered clearance parameters of cefonicid are the result of a flow-induced change in the intrinsic secretory transport of the drug.

Angiotensin II↗
PubMed1994

Patient- and treatment-related factors associated with acute regional toxicity after isolated perfusion for melanoma of the extremities.

In order to gain some insight into the cause of acute regional toxicity after isolated perfusion using melphalan, 15 patient-related and perfusion-technique-related factors were tested in a logistic regression model. Acute toxicity was graded according to Wieberdink's grading system. In a group of 425 patients, 362 (85%) encountered no or slight toxicity with a grade I or II reaction, and 63 (15%) patients encountered more severe toxicity with a grade III, IV, or V reaction. Most patients were treated with a standard dose of 10 or 13 mg melphalan per liter of perfused tissue for leg and arm perfusions, respectively. Factors associated with a more severe toxicity reaction proved to be tissue temperatures of 40 degrees C or higher, female gender, a deterioration of the gas values of the venous perfusate during perfusion, and perfusion at a proximal level of isolation. Consideration of these prognostic factors may lead to a further decrease of acute regional toxicity in perfusion.

Adult↗
PubMed1982

The effect of physostigmine on the vagally induced muscarinic inhibition of noradrenaline release from the isolated perfused rabbit atria.

1. Presynaptic cholinergic-adrenergic interactions were studied on isolated perfused rabbit atria with the extrinsic right vagus and sympathetic innervation intact. The transmitter stores were labelled with 14C-choline and 3H-noradrenaline. The radioactive compounds were separated on columns and determined by scintillation spectrometry. The stimulation-evoked overflow of both transmitters was calcium-dependent and abolished by tetrodotoxin. 2. Methacholine caused a concentration-dependent decrease of atrial tension development and 3H-noradrenaline overflow evoked by 3 Hz sympathetic stimulation. Vagus nerve stimulation (1-20 Hz), although nearly abolishing tension development at 20 Hz, decreased evoked 3H-noradrenaline overflow by not more than 18%. 3. Physostigmine decreased atrial cholinesterase activity by 80% and increased the fraction of stimulation-evoked unhydrolyzed 14C-acetylcholine in the persufates from 58 to 86%. However, the inhibition by vagus stimulation (1-10 Hz) of evoked 3H-noradrenaline overflow was smaller than in the absence of the drug. This was closely related to a decrease in acetylcholine overflow. Yet for a give fractional rate of acetylcholine release the muscarinic inhibition of noradrenaline overflow still did not exceed that observed in the absence of physostigmine. 4. It is concluded that the vagally induced control of noradrenaline release occurs at discrete sites rather than in a diffuse pattern at multiple terminal axon sites as is the case after exogenous muscarinic agonists.

Animals↗
PubMed1983

Time-dependent kinetics of lignocaine in the isolated perfused rat liver.

The kinetics of lignocaine have been investigated in the isolated perfused rat liver preparation. After a low dose (0.3 mg) the drug was eliminated according to first-order kinetics, but after higher doses (7.5, 15.0 mg) and multiple doses (3 X 1.5 mg at 15 min intervals), nonlinear kinetics were observed, which appeared to show time dependence. This was not due to deterioration of the preparation nor was there any evidence of a hepatotoxic effect of lignocaine. The kinetics of lignocaine were also found to be sex-dependent since it was eliminated at a faster rate by livers from male rats compared to those from female rats. Exogenous MEGX (7.5 mg), the mono-N-deethylated metabolite of lignocaine, inhibited the elimination of parent drug (1.5 mg dose). However, evidence was obtained suggesting that a direct effect of this and other end-product metabolites may not be responsible for the observed changes in lignocaine kinetics with time when the compounds are produced endogenously. Studies of the hepatic binding of lignocaine in the preparation showed the presence of high affinity-low capacity and low affinity-high capacity binding sites, which may be the enzymes responsible for aromatic hydroxylation and N-deethylation of the drug, respectively. Further experiments supported the view that an intermediate product of lignocaine, related to the N-deethylation pathway, might be inhibiting its further metabolism.

Animals↗
PubMed1986

The disposition of suramin in the isolated perfused rat liver.

We have investigated the disposition of suramin in the isolated perfused rat liver preparation (IPRL) after the administration of suramin (18 mg, 8 muCi). At 30 min post drug administration, almost 100% of the [14C]radioactivity and unchanged suramin were located in the perfusate plasma. During the course of the study, the elimination of suramin from the IPRL was barely perceptible. The AUC0-5 hr of suramin (730.6 +/- 86.2 micrograms hr/ml) corresponded to that of [14C] radioactivity (815.1 +/- 105.5 micrograms ml/hr) at 5 hr, indicating a lack of perfusate suramin metabolites. At 5 hr only a small proportion of [14C] radioactivity was recovered from the livers (2.5 +/- 1.1%). Subsequent HPLC analysis of the liver tissue indicated this to be unchanged suramin. Sub-cellular fractionation of the homogenised livers revealed suramin to be distributed in the liposomal rich tissue fractions (10,000 g pellet, 1.6 +/- 0.8%; 105,000 g supernatant, 1.1 +/- 0.35%). Biliary excretion of [14C] radioactivity was low (2.1 +/- 0.7%), however, none could be accounted for as unchanged suramin. Previously undetected metabolites of suramin may have accounted for the unidentified biliary radioactivity.

Animals↗
PubMed1988

Disposition of the antimalarial, mefloquine, in the isolated perfused rat liver.

The disposition of mefloquine has been investigated in the isolated perfused rat liver (IPRL) preparation after the administration of [14C]mefloquine HCl (3.8 mg, 4 microCi, quinoline ring labeled). Mefloquine underwent avid hepatic uptake within 10 min of dosing. Also at this point, hepatic oxygen consumption was reduced markedly in four of the six IPRL preparations, but was restored completely by approximately 30 min post-dose. The drug concentration profile underwent a biexponential decline over the 4-hr study period, with a terminal T1/2 of 1.0 +/- 0.3 hr. The area under the perfusate plasma concentration/time curve (AUC0-infinity) was 4.0 +/- 1.8 micrograms.hr.ml-1. Mefloquine was a high clearance compound (956.0 +/- 390 ml/hr) with a large apparent volume of distribution (1416 +/- 819 ml) in the IPRL. Biliary excretion accounted for 7.5 +/- 6.5% of the dose. Mefloquine was quantitated by HPLC analysis as approximately half (3.3 +/- 1.8%) of biliary label, the remainder consisting of highly polar metabolites of mefloquine. By 4 hr, a total of 64.8 +/- 4.4% of the [14C] dose was recovered from the livers. Subsequent HPLC analysis revealed this to be mostly unchanged mefloquine. Subcellular fractionation of the homogenized livers revealed that 50.6 +/- 6.8% of the dose of mefloquine was located in the 10,000 g pellet. In summary, mefloquine was cleared rapidly from the IPRL and underwent avid hepatic uptake into the lipid-rich fractions of rat liver.

Animals↗
PubMed1983

Uptake of metabolism of norepinephrine in isolated perfused fetal, newborn and adult rabbit lungs.

We compared the ability of isolated perfused lungs from previable, 26-day gestation, fetal rabbits; newborn rabbits (within 12 hours of birth) and 3 month old adult rabbits to metabolize a 20-second bolus of norepinephrine (NE). The concentration of NE infused was much below the Km for the NE uptake process to assure first order uptake kinetics. At these low concentrations no vasoactivity was observed. The retention time of a vascular marker dye was monitored as an index of pulmonary vascular surface area. In all three sizes of lungs perfusate flow was adjusted to produce an approximately 7 second dye retention time. At these flow adult and newborn lungs inactivate about 50 to 60 percent of the infused NE. In contrast, fetal rabbit lungs inactivate about 80 percent of the infused NE. We conclude that circulating NE is most avidly taken up and metabolized during fetal lung development. The physiologic significance of this fetal NE inactivation remains unknown.

Age Factors↗
PubMed1977

The transfer of estrone glucuronide to bile in an isolated perfused rat liver system.

An isolated rat liver perfusion system has been utilized in a study of the biliary excretion of estrone glucuronide. The estrogen was initially shown to be excreted without prior metabolism. Disappearance from the medium was rapid and biliary concentrations exceeded that in the medium by more than a thousand-fold. Disappearance rates were decreased when medium estrone glucuronide concentrations exceeded 0.29 mM. Inhibition by other steroidal conjugates, testosterone glucuronide, 2-methoxyestrone (3-hydroxy-2-methoxy-estra-1,3,5(10)-trien-17-one glucuronide and 2-hydroxyestrone (2,3-dihydroxyestra-1,3,5(10)-trien-17-one) glutathione, was also demonstrated. Phenolphthalein glucuronide, at 10 times the molar concentration of estrone glucuronide, did not affect the medium clearance of the latter compound. These findings indicate the possibility of utilizing this system for further studies of possible interactions by other organic compounds for excretion via the biliary route.

Animals↗
PubMed1982

Evidence for different localization of glutathione oxidase and gamma-glutamyltransferase activities during extracellular glutathione metabolism in isolated perfused rat kidney.

The metabolism of extracellular glutathione was studied in the isolated, perfused rat kidney. The results indicate different localization of glutathione oxidase and gamma -glutamyltransferase (5-glutamyl)-peptide: aminoacid 5-glutamyltransferase, EC 2.3.2.2) activities, since glutathione oxidase activity was observed only with glutathione present in the perfusate, whereas gamma -glutamyltransferase-mediated metabolism of glutathione was restricted to glutathione present to the localization of renal gamma -glutamyltransferase in the brush border membranes of the tubular epithelium, but suggest an opposite localization of renal glutathione oxidase activity, i.e., in the basal plasma membrane fraction of the tubular cells, facing the capillary bloodstream. Furthermore, the existence of the tubular glutathione extraction mechanism operating in addition to glomerular filtration is confirmed.

Animals↗