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PubMed1996

Dynamic lymphoscintigraphy to identify the sentinel and satellite nodes.

Lymphoscintigraphy is increasingly used to identify the first draining node (sentinel node) in patients with malignant melanoma or breast cancer. If the sentinel node is tumor free then the remainder of the nodes in that specific nodal bed are likely to be free of metastases. Localization and biopsy of the sentinel node with an intraoperative surgical probe may obviate more radical lymph node dissection. Lymphoscintigraphy is conventionally performed by injecting the radioactive tracer in the four quadrants around the primary tumor and imaging the appropriate nodal beds approximately 30 minutes later. The visualized node nearest the tumor usually is assumed to represent the sentinel node. To test this assumption, a dynamic acquisition was obtained in 16 patients with malignant melanoma to determine if the node nearest the tumor was actually the first draining node. In one of 16 patients, the radioactive tracer injected around a thigh melanoma drained first to an inguinal node and then drained inferiorly to a second inguinal node located closer to the tumor. The distinction between the sentinel and satellite (secondary draining nodes) may have important clinical implications regarding the number of nodes that require surgical excision. In summary, static images do not define the pattern of lymph flow and the node nearest the tumor is not necessarily the sentinel node. Failure to obtain dynamic images may lead to misdiagnosis of the sentinel node in a small percentage of patients.

Humans↗
PubMed1992

Potency of depolarization-induced transmitter release is determined by divalent cation influx in PC 12 cells.

Evoked release of [3H]dopamine ([3H]DA) from pheochromocytoma cells (PC 12) is dependent on extracellular calcium ([Ca2+]ex), but it can take place if calcium ions (Ca2+) are substituted by other divalent ions such as strontium (Sr2+) and barium (Ba2+). The potency of the divalent cations at supporting release varies with the cell type; in PC 12 cells the order of potency is Ba2+ > Sr2+ > Ca2+. The close correlation between depolarization-evoked Ca2+ entry and depolarization-evoked transmitter release prompted us to examine whether the higher evoked transmitter release in the presence of Sr2+ correlates with an increased evoked Sr2+ influx. Influx studies were conducted on PC12 cells using a radioactive tracer (45Ca2+ or 85Sr2+, < 1 microM) in the presence of either Sr2+ (0.5 mM) or Ca2+ (0.5 mM). Depolarization with K Cl (60 mM) increased evoked 45Ca2+ influx 2-fold when Ca2+ was substituted with Sr2+. Similarly, evoked 85Sr2+ influx increased 1.87-fold by substituting Ca2+ for Sr2+. Thus the amount of evoked cation influx is determined by the type of divalent ion which is accessible in the extracellular medium, independently of the radioactive tracer used. Increased evoked transmitter release in the presence of Sr2+ was associated with increased evoked Sr2+ influx. This suggests that the potency of evoked transmitter release is determined predominantly by the influx of divalent cations. Furthermore, the steps subsequent to cation influx in the release process are equally efficient for both cations.

Animals↗
PubMed1986

Cellular sodium transport in arterial wall--summary of studies by digital computer simulation.

The distribution of electrolytes between extracellular and intracellular compartments is of greater functional significance in biological tissues than the total amount. A method commonly employed for the study of a substance distribution among different spaces is the continuous outflow and radioisotope counting of a fragment of tissue previously incubated with a radioactive tracer (here 22Na+). The experimental data can be analyzed within the frame of a compartmental analysis system which is defined by transport rate constants (kij) and solved when all kij are numerically determined. In practical applications the direct solution requires measurements in different compartments or knowledge of the initial condition for each compartment, but this is not possible in most biological tissues where the experimentally observable data represent the summation of tracer in all compartments at each point in time. The availability of the SAAM (Simulation, Analysis And Modelling) computer program allows for a powerful simulation procedure to arrive at values for kij. Experimental data and specifications for a chosen model are entered in the SAAM format. A simulated 'inflow' experiment is made by the computer by assigning to kij some estimate values. All initial conditions are now zero, since at the beginning there is no radioactive tracer in any compartment. After a time equivalent in the experimental realm to achieving constant specific activity, a 'time change' programmed into the computer takes place so that the outflow part of the experiment is developed with the same kij as for the inflow part, the final conditions for the inflow before the time change being the initial conditions for the outflow. An iterative procedure modifies the initial estimates of kij to seek the best fit. By coupling a powerful simulation procedure to an advanced radionuclide tracer biological methodology, we have been able to find effects of the hormone aldosterone and of experimental hypertension on Na+ distribution in arterial wall years before such effects were demonstrated by purely conventional experimental techniques. This computer simulation procedure may be suited to other experimental situations in which outflow data are the only available.

Aldosterone↗
PubMed1976

Myocardial imaging in the noninvasive evaluation of patients with suspected ischemic heart disease.

Three noninvasive radioactive tracer techniques for evaluating patients with ischemic heart disease are described: (1) myocaridal perfusion imaging, (2) acute infarct imaging, and (3) the gated blood pool scan. Myocardial perfusion imaging with tracers that distribute in the myocardium in relation to regional blood flow allows detection of patients with transmural and nontransmural infarction by the finding of decreased tracer concentration in the affected region of the myocardium. If these tracers are injected at the time of maximal stress to patients with significant coronary arterial stenosis but without infarction, areas of transient ischemia can be identified as zones of decreased tracer concentration not found when an examination is performed at rest. Acute infarct imaging with tracers that localize in acutely damaged tissue permits separation of patients with acute myocardial necrosis from those without infarction and those with more chronic damage. The gated blood pool scan permits assessment of left ventricular function and regional wall motion. The measurement of ventricular volumes, ejection fraction and regional wall motion adds significantly to the determination of hemodynamic variables in assessing patients with acute infarction. The technique also permits detection of right ventricular dysfunction. Performance of a combination of these radioactive tracer techniques is often advantageous, particularly in patients with suspected infarction. The techniques can establish whether infarction is present, whether it is acute, where the damage is located and how extensive it is; they can also provide a measure of the effect of this damage on left ventricular function.

Acute Disease↗
PubMed1989

[Diagnostic strategies in liver and pancreatic tumors using imaging procedures--nuclear medicine].

The different biokinetic behaviour of radioactive tracers which can be monitored by nuclear medicine procedures may be helpful in the diagnosis or differential diagnosis of tumours or tumour-like lesions of the liver or pancreas: autologous red blood cells in the detection of haemangiomas; iminodiacetates in delineation of focal nodular hyperplasia, resp. liver adenomas versus other tumours; colloidal albumin in differentiating focal fatty infiltration from diffuse infiltration by metastases; monoclonal antibodies in revealing liver metastases or abscesses, resp. pancreas neoplasms. In general the clinical suspected diagnosis and the result of morphologic imaging modalities determine the use of the appropriate radioactive tracers.

Adenoma↗
PubMed1980

Microprobe study of toad urinary bladder in absence of serosal K+.

The bulk of the intracellular potassium in mucosal epithelial cells from toad urinary bladder has been previously reported to exchange very slowly with the serosal medium, with a half-time of some 9 hr. This observation, based on chemical analyses of mucosal cell scrapings, has been reexamined with stimultaneous diffractive and energy dispersive electron probe X-ray microanalysis. Fifty-three intracellular sites in hydrated sections and 286 sites in dehydrated sections were studied in bladders from eight toads under baseline conditions and after removal of serosal K+ for 83-133 min, with or without 10(-2) M ouabain. The baseline data confirm and extend previous examinations of the intracellular ionic composition, and provide the most direct measure of intracellular water thus far available for this tissue. Removal of serosal K+ reduced the intracellular K+ content by 20%, increased intracellular Na+ content threefold, and slightly reduced the intracellular Cl- and water contents, qualitatively consistent with published chemical analyses. The intracellular Na+ content of mucosal origin, measured by radioactive tracers and chemical analyses of cell scrapings, has been reported to be unchanged under these conditions. Simultaneous addition of ouabain and removal of external K+ produced a dramatic fall in intracellular K+ of more than 80% in a third of the cells and reduced the mean intracellular K+ content by 60%; 20% of the cells appeared to retain K+ more effectively than the bulk of the epithelial cell population. We conclude that: (i) the low rate of net exchange of intracellular K+ with the serosal bulk solution primarily reflects recycling of K+ across the basolateral membranes, (ii) radioactive tracer and chemical measurements of the intracellular Na+ pool of mucosal origin substantially understimate the total intracellular Na+ content under certain experimental conditions, and (iii) the epithelial cells display a functional heterogeneity of response to the effects of adding ouabain and withdrawing external K+.

Animals↗
PubMed1989

A review of water diffusion measurement by NMR in human red blood cells.

This review of water transport measurement in normal human erythrocytes attempts to harmonize discordant results obtained under diverse study conditions with two different techniques: nuclear magnetic resonance (NMR) and radioactive tracer (THO) diffusion. Natural aggregation of red cells into rouleaux appeared to cause most of the variation among results from NMR experiments. The remainder of the discrepancy was attributed to the use of inappropriate mathematical approximations of the two-site exchange equations, differences in blood storage time, and failure to adjust NMR calculations for the nonwater protons. Differences in hematocrit, frequency-magnetic field strength, or NMR pulse technique played no apparent role in the disparity among NMR reports. When these confounding factors were removed, diffusion results obtained by NMR or by influx or bulk diffusion of radioactive tracer agreed within a relatively narrow range of values. These techniques place the mean lifetime of water inside fresh normal human erythrocytes at room temperature (20-25 degrees C) between the extremes of 9.8 and 14 ms, where the uncorrected range was previously 9.8-21.7 ms. This new range of water exchange times corresponds to a range of diffusional permeability between 3.3 and 4.7 x 10(-3) cm/s.

Body Water↗
PubMed1991

A novel cell-permeable cromoglycate derivative inhibits type I Fc epsilon receptor mediated Ca2+ influx and mediator secretion in rat mucosal mast cells.

Type I Fc epsilon receptor (Fc epsilon RI) mediated Ca2+ uptake and secretion of rat serosal mast cells have been shown to be inhibited by disodium 1,3-bis [(2'-carboxylatochromon-5'-yl) oxy]-2-hydroxypropane (disodium cromoglycate, DSCG), which is widely employed in the treatment of allergic asthma [Foreman et al. (1977) Br. J. Pharmacol. 59, 473P-474P; Cox (1967) Nature (London) 216, 1328-1329]. This drug was also found to modify the protein phosphorylation pattern of these mast cells. [Theoharides et al. (1980) Science 207, 80-82]. We have isolated by affinity chromatography on a water-insoluble cromoglycate-carrying matrix a cytosolic enzyme recently identified as a nucleoside 5'-diphosphate kinase. In order to examine a possible intracellular activity of the drug, a cell-permeant cromoglycate derivative, 1,3-bis [[2'-[[(acetoxymethyl)oxy]carbonyl]chromon-5'- yl]oxy]-2-hydroxypropane [bis(acetoxymethyl) cromoglycate, CG/AM], has been synthesized, and its uptake and effect on the Fc epsilon RI-mediated exocytosis of mast cells was investigated. A tritium-labeled CG/AM derivative, used as radioactive tracer, was found to permeate mucosal mast cells of the rat line RBL-2H3 and accumulate intracellularly up to 40-fold its extracellular concentration following hydrolysis by cytoplasmic hydrolases. A CG/AM dose dependent inhibition of the Fc epsilon RI-induced mediator secretion was observed in RBL-2H3 cells loaded with this compound (I50 approximately 40 microM extracellular CG/AM). A similar dose-dependent inhibition was observed for both the Fc epsilon RI-mediated transient rise in the concentration of cytosolic free Ca2+ ions [( Ca2+]i) and the net Ca2+ influx, as monitored by the fluorescent indicator Quin2 and the radioactive tracer 45Ca2+, respectively. These results clearly show that cell-permeant cromoglycate inhibits the Fc epsilon RI-mediated Ca2+ influx into the cell and further underscore the dominant role of this process in the coupling of stimulus to secretion in RBL cells. Furthermore, with the identification of nucleoside 5'-diphosphate kinase as a potential intracellular target for CG activity, distinct mechanisms of action may be inferred for cell-permeant and nonpermeant forms of CG.

Animals↗
PubMed2001

Kinetics of coaggregation of Porphyromonas gingivalis with Fusobacterium nucleatum using an automated microtiter plate assay.

Coaggregation between Porphyromonas gingivalis and Fusobacterium nucleatum strains was previously studied using either a semi-quantitative macroscopic assay or radioactive tracer assays. A new automated microtiter plate assay is introduced, in which the plate reader (Vmax) was adapted to allow quantitative evaluation of the kinetics of coaggregation. F nucleatum PK 1594 coaggregated with P. gingivalis HG 405 with a maximal coaggregation rate of 1.05 mOD/min, which occurred at a P. gingivalis to F. nucleatum cell ratio of 1 to 2. F. nucleatum PK 1594 failed to do so with P. gingivalis strains A 7436 or ATCC 33277. Galactose inhibition of this coaggregation could be quantitatively measured over a wide range of concentrations to demonstrate its dose-dependent manner. P. gingivalis HG 405 failed to coaggregate with F. nucleatum strains ATCC 25586 and ATCC 49256. The assay used in the present study is a sensitive and efficient quantitative automated tool to study coaggregation and may replace tedious radioactive tracer assays.

Automation↗
PubMed2001

A new radiocolloid for sentinel node detection in breast cancer.

BACKGROUND: The optimal radioactive tracer and technique for sentinel lymph node localization in breast cancer is yet to be determined. The dilemma of small particle size with dispersion to second echelon nodes versus failure of migration of larger radiocolloids needs to be resolved. A new radiocolloid preparation with particle size under 0.1 micron was developed with excellent primary/post lymphatic entrapment ratio. OBJECTIVE: To assess the feasibility of a new 99mTc radiocolloid cysteine-rhenium colloid in sentinel lymph node (SLN) localization for breast cancer. METHODS: Forty-seven patients with newly diagnosed T1 or T2 breast cancer underwent injection of 99mTc-labeled cysteine-rhenium colloid followed by lymphoscintigraphy. Same day SLN biopsy with patent blue dye and intraoperative gamma probe to identify SLNs were performed. RESULTS: SLN mapping and intraoperative localization were successful in 46/47 (98%) of patients. The blue dye radioactive tracer concordance was 94%. There was one false-negative in a patient with a nonpalpable tumor that underwent ultrasound-guided peritumoral radiocolloid injection. CONCLUSIONS: 99mTc-cysteine-rhenium colloid is highly effective in identifying SLNs. It has the advantage of smaller particle size than sulfur colloid with easier lymphatic migration. It has a more neutral pH with less pain on injection and does not require filtration, thereby minimizing radiation exposure to technologists.

Animals↗
PubMed1992

Modulation of ion transport in cultured rabbit tracheal epithelium by lipoxygenase metabolites.

Lipoxygenase metabolites influence ion movement and fluid balance in the airways. We studied the effects of nordihydroguaiaretic acid (NDGA), a general inhibitor of the lipoxygenase pathway, on Na+ and Cl- secretion in cultured tracheal epithelial cells from adult rabbits through short-circuit current (Isc) and radioactive tracer flux experiments. NDGA inhibition of leukotriene release in freshly isolated rabbit tracheal epithelial cells was assayed by a 3H peptidyl-leukotriene radioimmunoassay. 3 microM NDGA resulted in a 91% reduction of leukotriene release. In unstimulated cultures, Cl- secretion (furosemide-inhibited fraction of Isc) was 11.1 +/- 2.8 muamp/cm2 (n = 10) and was unchanged in the presence of NDGA (n = 10). Epinephrine-stimulated Cl- secretion increased Isc by 12.2 +/- 2 muamp/cm2 (n = 10). This stimulation was unchanged by pretreatment with NDGA (n = 10), suggesting that inhibition of the lipoxygenase pathway did not affect Cl- secretion. In unstimulated cultures, Na+ absorption (amiloride-inhibited portion of Isc) was 10.7 +/- 3.3. muamp/cm2 (n = 10) and was reduced by 79% in the presence of NDGA (n = 10), suggesting that inhibition of the lipoxygenase pathway was associated with inhibition of Na+ absorption. Radioactive tracer flux experiments supported these findings. Exogenous LTD4 (n = 7) and LTC4 (n = 7) were added to cells pretreated with NDGA, and Na+ absorption was restored to 76% and 70% of control, respectively. In addition, LTD4 (n = 4) and LTC4 (n = 4) were added to cells without prior inhibition of the lipoxygenase pathway to NDGA and resulted in an increase in Cl- secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride↗
PubMed2001

Characterization and modeling of the metal diffusion from deep ultraviolet photoresist and silicon-based substrate.

The radioactive tracer technique was applied to investigate the out-diffusion of the transition metals (Cu, Fe and Co) from deep ultraviolet (DUV) photoresist into underlying substrate. Two important process parameters, viz., baking temperatures and substrate types (i.e., bare silicon, polysilicon, silicon oxide and silicon nitride), were evaluated. Results indicate that the out-diffusion of Co is insignificant, irrespective of the substrate type and baking temperature. The out-diffusion of Cu is significant for substrates of bare silicon and polysilicon but not for silicon oxide and nitride; for Fe, the story is reversed. The substrate type appears to strongly affect the diffusion, while the baking temperature does not. Also, the effect of solvent evaporation was found to play an important role in impurity diffusion. Using the method of numerical analysis, a diffusion profile was depicted in this work to describe the out-diffusion of metallic impurities from photoresist layer under various baking conditions. In addition, the effectiveness of various wet-cleaning recipes in removing metallic impurities such as Cu, Fe and Co was also studied using the radioactive tracer technique. Among the six cleaning solutions studied, SC2 and SPM are the most effective in impurity removal. An out-diffusion cleaning model was first proposed to describe the cleaning process. A new cleaning coefficient, h(T), was suggested to explain the cleaning effect. The cleaning model could explain the tracer results.

Journal Article↗
PubMed1973

Microbial metabolism of amino alcohols. 1-Aminopropan-2-ol and ethanolamine metabolism via propionaldehyde and acetaldehyde in a species of Pseudomonas.

1. Growth and manometric experiments showed that a Pseudomonas sp. P6 (N.C.I.B. 10431), formerly known as Achromobacter sp. P6, was capable of growth on both stereoisomers of 1-aminopropan-2-ol, and supported the hypothesis that assimilation involved metabolism to propionaldehyde, propionate and possibly 2-hydroxyglutarate. A number of alternative intermediary metabolites were ruled out. 2. Accumulation of propionaldehyde from 1-aminopropan-2-ol by intact cells occurred only during active growth, was transitory and was accompanied by morphological changes in the pseudomonad. 3. Enzymic and radioactive tracer evidence showed that 1-aminopropan-2-ol O-phosphate was the intermediate between amino alcohol and aldehyde. The operation of an inducibly formed ATP-amino alcohol phosphotransferase was established by measuring substrate disappearance, ADP formation and amino alcohol O-phosphate formation. This novel kinase had two activity peaks at about pH7 and 9. It acted on both l- and d-isomers of 1-aminopropan-2-ol, and also on l-threonine and ethanolamine, but had only low activity towards choline. The enzyme was partially purified by ion-exchange chromatography. 4. An amino alcohol O-phosphate phospho-lyase (deaminating) produced propionaldehyde from dl- and d-1-aminopropan-2-ol O-phosphate, and also formed acetaldehyde less rapidly from ethanolamine O-phosphate. It had optimum activity at about pH8 in Tris-HCl buffers. The enzyme was partially purified and evidence was obtained that a single enzyme was responsible for both activities. Apparent K(m) values for the substrates were determined. Activity was inhibited by dl-threonine O-phosphate, dl-serine O-phosphate, choline O-phosphate and P(i). Enzyme formation was induced by growth with either amino alcohol substrate. 5. Radioactive tracer experiments with dl-1-amino[3-(14)C]propan-2-ol confirmed the operation of the amino alcohol kinase and demonstrated coupling with the phospho-lyase enzyme in vitro to produce [(14)C]-propionaldehyde. 6. An aldehyde dehydrogenase, found in extracts of the pseudomonad after growth on 1-aminopropan-2-ol, was characterized and concluded to be responsible for propionaldehyde and acetaldehyde oxidation. The enzyme was inactive with methylglyoxal. 7. Propionate and acetate were concluded to be metabolized via propionyl-CoA and acetyl-CoA, and studies were made of a CoA ester synthase found in extracts. 8. Studies of a strain of Pseudomonas putida N.C.I.B. 10558 suggested that 1-aminopropan-2-ols were metabolized via their O-phosphates, propionaldehyde and propionate. Amino alcohol kinase activity was detected and extracts contained a phospho-lyase showing higher activity with the 1-aminopropan-2-ol O-phosphate than with ethanolamine O-phosphate.

1-Propanol↗
PubMed1999

Response to 45 degrees head-down tilt as measured by organ weight/body weight ratios and spiral computed tomography.

BACKGROUND: Exposure to microgravity or simulated microgravity causes significant shifts in body fluids which may initiate physiological adaptations to the microgravity stressor. It is imperative to understand the physiological adaptations to microgravity in order to develop appropriate countermeasures to the deleterious aspects (i.e., muscle and bone wasting) of long-term spaceflights. HYPOTHESIS: The significant shifts in body fluids by 45 degrees head-down tilt can be measured by changes in organ weight/body weight (OW/BW) ratios and non-invasively by spiral computed tomography. METHODS: In a previous study (14), rats were weighed and exposed to either 45 degrees head-down tilt (45HDT) or a prone control position for one of the following experimental times: 0.5 h, 1 h, 2 h, 4 h, 8 h, or 24 h. A radioactive tracer was injected intramuscularly immediately prior to the start of the experimental time periods. At the end of the experiment, the major organs were harvested, weighed, and measured for gamma radiation levels. We used the organ weights from this previous study to calculate OW/BW ratios for the present study. Additionally, in the present study, rats in the 14-d experimental groups were weighed, lightly anesthetized to facilitate placement in the 45HDT position, and placed in a specially designed 45HDT cage (45HDT group) or left unrestrained in the cages (control group). At the end of the 14-d experimental time period, the rats were anesthetized and their lung densities measured with spiral computed tomography. RESULTS: The OW/BW ratios for the liver, kidneys, and spleen of 24 h 45HDT rats were significantly lower (p<0.05) than control values while at 1 h the 45HDT rats had a higher kidney OW/BW ratio. Lung density from the 14-d 45HDT rats was 24.4% greater than control rats' values. CONCLUSIONS: The physiological change due to the 45HDT position to simulate microgravity begins as early as 1 h, and the kidney appears to be the first organ affected. Spiral computed tomography may offer a viable method of non-invasively measuring organ densities in the 45HDT model. The OW/BW data generated in the present study does not correlate with the changes in radioactive tracer distribution data from our previous study.

Adaptation, Physiological↗
PubMedDate not supplied

Intradermal isotope injection: a highly accurate method of lymphatic mapping in breast carcinoma.

BACKGROUND: The combined approach of radioactive tracer and blue-dye mapping of sentinel lymph nodes (SLN) has evolved into a safe and effective alternative to routine axillary node dissection in specific patient populations with breast carcinoma. The optimal route of injection for the isotope has not been clearly defined. To assess the intradermal route of isotope injection, we prospectively evaluated 100 patients with biopsy-proven invasive breast carcinoma with SLN biopsy followed by planned axillary node dissection. METHODS: All patients were given an intradermal injection of Tc-99m sulfur colloid and an intraparenchymal injection of blue dye. All patients underwent a complete axillary node dissection. Each sentinel node was serially sectioned and examined by immunohistochemistry. RESULTS: Sentinel nodes were successfully identified in 99% of cases. Forty-six patients had axillary metastases; of these, four had falsely negative sentinel nodes (false-negative rate, 9%). The false-negative rate was 0 of 24 (0%) for T1 tumors, 2 of 18 (11%) for T2 tumors, and 2 of 4 (50%) for T3 tumors. Three of four patients with false negatives had palpable, clinically suspicious axillary nodes found intraoperatively. If these cases are excluded, the accuracy of the procedure was 100% for T1 and T2 tumors. Of the 42 positive axillae identified by SLNB (true positives), 40 were localized using the intradermal injection of radioisotope; in 13 of these cases, this was the only method that identified the true-positive node. CONCLUSION: These data demonstrate that intradermal injection of radioactive tracer is an effective method of localizing the SLN in cases involving small breast cancers. Further investigation is warranted before this technique is adopted for use in larger breast cancers. Intraoperative examination and biopsy of any suspicious nonsentinel nodes are critical.

Adult↗
PubMed1982

Bile acid transport in cultured rat hepatocytes.

The mechanisms of bile acid uptake have been studied with primary monolayer cultures of rat hepatocytes. Hepatocytes were incubated with taurocholic acid (TC), glycocholic acid (GC), cholic acid (CA), glycochenodeoxycholic acid (GCDC), chenodeoxycholic acid (CDCA), deoxycholic acid (DOCA), lithocholic acid (LCA), or cholylglycylhistamine (CCH), a neutral bile acid derivative for 10 s to 60 min in medium containing sodium chloride, sodium chloride with 1 mM ouabain, or choline chloride. Cells were washed free of radioactive tracer, cell-associated radioactivity was quantitated, and bile acid uptake rates, kinetic parameters of uptake, and steady-state bile acid content were calculated. Two mechanisms for bile acid uptake were identified. Uptake of TC, GC, CA, and GCDC occurred predominantly via a sodium-dependent, ouabain-suppressible saturable mechanism, presumably sodium-coupled transport. Estimates of apparent Km and Vmax for these bile acids were TC, 33 micro M and 0.36 nmol . min-1 . mg prot-1; GC, 18 micro M and 0.22 nmol . min-1 . mg prot-1; CA, 13 micro M and 0.10 nmol . min-1 . mg prot; and GCDC, 6 micro M and 0.21 nmol . min-1 . mg prot, respectively. Uptake via this sodium-coupled mechanism exhibited considerable substrate selectivity. It was enhanced by increased ring hydroxylation and amino acid conjugation and decreased by further conjugation with a neutral histamine group (CGH). In contrast, uptake of CDCA, DOCA, LCA, and CGH occurred primarily via a nonsaturable sodium-independent mechanism, possibly simple diffusion. This mechanism accounted for only a small portion of uptake of TC, GC, CA, and GCDC at low bile acid concentrations. Nonsaturable bile acid uptake rates appeared to correlate with decane-buffer partition coefficients and to be related to bile acid structure.

Animals↗