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R Bruck

Publications and source records attributed to R Bruck.

15 recordsLinked to original sources
PubMed1992

Effects of Ca2+ agonists on cytosolic Ca2+ in isolated hepatocytes and on bile secretion in the isolated perfused rat liver.

The effects of increases in cytosolic Ca2+ on hepatocyte bile secretion are unknown. A number of agents that alter levels of cytosolic Ca2+ in the hepatocyte also produce hepatic vasoconstriction and activate protein kinase C, which complicates interpretations of their effects on bile secretion. To better understand the role of cytosolic Ca2+ in bile secretion, we examined the effect of the Ca2+ ionophore A23187 (0.1 mumol/L), the Ca2+ agonist vasopressin (10 nmol/L) and the Ca(2+)-mobilizing agent, 2,5-di(tert-butyl)-1,4-benzohydroquinone (25 mumol/L) on cytosolic Ca2+ in isolated hepatocytes and on bile flow in the isolated perfused rat liver, using vasodilators and inhibitors of protein kinase C and Ca2+ influx. Single-pass perfused livers were used, and cytosolic Ca2+ was measured by luminescent photometry in isolated hepatocytes loaded with the Ca(2+)-sensitive photoprotein aequorin. After A23187 perfusion, a sustained 74% +/- 10% (mean +/- S.D.) decrease in bile flow and a sustained 271% +/- 50% increase in perfusion pressure was observed. Simultaneous pretreatment with the vasodilator papaverine (25 mumol/L) and the protein kinase C inhibitor H-7 (50 mumol/L) abolished the pressure increase but not the decrease in bile flow, whereas pretreatment with Ni2+ (25 mumol/L) to block the influx of extracellular Ca2+ markedly reduced both the pressure increase and the decrease in bile flow. Vasopressin produced a transient (mean = 6 min) 75% +/- 4% decrease in bile flow and a sustained 7% +/- 4% increase in perfusion pressure. Pretreatment with H-7 alone corrected the vasopressin-induced pressure increase but also failed to eliminate the decrease in bile flow, whereas pretreatment with Ni2+ decreased the magnitude of the decrease by two-thirds without affecting the increase in perfusion pressure, 2,5'-di(tert-butyl)-1,4-benzohydroquinone produced a transient 65% +/- 20% decrease in bile flow and a transient 56% +/- 15% increase in perfusion pressure. In isolated hepatocytes, bromo-A23187, the nonfluorescent form of the ionophore, produced a sustained 56% +/- 32% increase in the cytosolic Ca2+ signal, whereas vasopressin resulted in a transient 241% +/- 75% increase and 2,5-di(tert-butyl)-1,4-benzohydroquinone resulted in a sustained 149% +/- 66% increase. The ionophore-induced increase in Ca2+ was abolished completely by pretreatment of the hepatocytes with Ni2+, whereas the vasopressin-induced increase was reduced by 38%.(ABSTRACT TRUNCATED AT 400 WORDS)

Aequorin↗
PubMed1992

Regulatory volume decrease stimulates bile flow, bile acid excretion, and exocytosis in isolated perfused rat liver.

To study the effect of volume regulation on bile secretory function, isolated perfused rat livers (IPRL) were exposed to hypotonic stress (45 mM NaCl) while bile flow and the biliary excretion of bile acids and horseradish peroxidase (HRP) were assessed. Hypotonic stress induced a biphasic increase in bile flow, which rose in the first minute from 1.1 +/- 0.2 to 1.7 +/- 0.1 microliter.min-1.g liver-1 (P less than 0.01), an effect attributed to rapid osmotic equilibration of water, then increased further between 3 and 5 min to 1.6 +/- 0.1 microliter.min-1.g liver-1 (P less than 0.01, followed by a subsequent return to baseline. HRP excretion in bile increased during the second peak of bile flow from 0.9 +/- 0.2 to 1.1 +/- 0.2 ng.min-1.g liver-1, P less than 0.01. Pretreatment with colchicine but not lumicolchicine completely abolished the latter increase in bile flow and HRP excretion as did BaCl2 (1 mM), an inhibitor of both K+ channels and regulatory volume decrease (RVD) in hepatocytes. When sodium taurocholate was infused (1 mumol/min), hypotonic stress induced an even larger increase in the second peak of bile flow (5.1 +/- 0.7 microliters/g liver, P less than 0.01) and higher rates of bile acid excretion than in control perfusions with bile acid (126.2 +/- 21.0 vs. 99.0 +/- 17.1 nmol.min-1.g liver-1, P less than 0.05). These data suggest that both bile flow and bile acid excretion are stimulated during RVD by mechanisms that involve both K+ channels and microtubule-dependent exocytosis at the canalicular (apical) membrane domain.

Animals↗
PubMed1992

Hormonal regulation of paracellular permeability in isolated rat hepatocyte couplets.

Many hormones and drugs exert their effects on cells by increasing cytosolic Ca2+ (Cai2+) and activating protein kinase C (PKC). Each of these actions results in cholestasis in the isolated perfused rat liver, but the responsible mechanisms are unclear. We used isolated rat hepatocyte couplets to observe the direct effects of increased Cai2+ and PKC activation on permeability of the hepatocyte tight junction and canalicular volume, two possible determinants of hepatocyte bile secretion. Couplets were stimulated with the Ca2+ agonist vasopressin (10(-8) M) in the absence and presence of the Ca2+ influx antagonist Ni2+ (5 x 10(-3) M) or with the PKC activator phorbol dibutyrate (10(-6) M). Cai2+ was determined by ratio microspectrofluorometry of indo-1, permeability of the couplet tight junctions was assessed by exclusion of horseradish peroxidase from the canalicular space, and changes in canalicular volume over time were measured directly by optical planimetry. Canalicular volume increased by 1.6 +/- 2.5%/min (mean +/- SD) under basal conditions. In response to vasopressin, there was a rapid 15-fold increase in Cai2+, followed first by an increase in paracellular permeability, then by canalicular collapse (15.9 +/- 5.9%/min). Pretreatment with Ni2+ markedly decreased the vasopressin-induced increase in Cai2+ and abolished both the increase in paracellular permeability and the canalicular collapse. Phorbol dibutyrate also increased paracellular permeability but resulted in neither increased Cai2+ nor canalicular collapse. The PKC inhibitor H-7 reversed the effects of both vasopressin and phorbol dibutyrate on tight junction permeability. Bile secretory pressure, measured in isolated perfused rat liver preparations, was acutely increased by vasopressin, but the increase was augmented rather than inhibited by Ni2+.(ABSTRACT TRUNCATED AT 250 WORDS)

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1991

Vanadate inhibits glucose output from isolated perfused rat liver.

Previous studies have demonstrated that vanadate ions mimic many of the actions of insulin in in vitro systems. Also, vanadate administered to diabetic hyperglycemic rats lowers their blood glucose levels to normal values. In this study we demonstrate that vanadate inhibits glucose output in the isolated perfused rat liver. Glucose production was suppressed maximally (about 50% to 60%), on addition of extremely low vanadate ion concentrations (0.5 to 1 mumol/L). This concentration is about two log units lower than the vanadate ion concentrations that are required to activate hexose uptake and glucose metabolism in vitro and is within the range of endogenous intracellular vanadium concentration. Insulin had little or no effect in inhibiting hepatic glucose output in this experimental system. The effect of vanadate ions is rapid in onset and is not accompanied by any signs of liver toxicity as assessed by various criteria. In conclusion, the study indicates that (a) vanadate ions inhibits hepatic glucose output, maximally and at extremely low, nontoxic concentrations (ID50 = 0.7 +/- 0.1 mumol/L). (b) The modulation action of the ion is fast and probably occurs at point(s) distal to the insulin receptor itself. (c) The liver participates in the process of maintaining euglycemia in diabetic rats receiving optimal doses of vanadate orally.

Animals↗
PubMed1990

Cimetidine and omeprazole have different effects on hepatic extraction of lidocaine in rats.

The effect of two antisecretory drugs, omeprazole and cimetidine, on the hepatic extraction of indocyanine green and lidocaine was studied in the isolated perfused rat liver. Both indocyanine green and lidocaine are removed by the liver with high extraction efficiency in a flow-dependent manner. The elimination of lidocaine, but not indocyanine green, involves metabolism by the mixed-function oxidase in the liver. A selective effect on the hepatic extraction of lidocaine, but not indocyanine green, may therefore indicate an inhibition of hepatic mixed-function oxidase. To test this hypothesis, a nonrecycling system at a fixed perfusion flow rate was used to measure the extraction of lidocaine. Under control conditions, the extraction rate of lidocaine was 83% +/- 8%. In the presence of omeprazole at concentrations of 0.9, 2.0, and 4.5 micrograms/mL, the extraction rates were 81% +/- 9%, 82% +/- 7%, and 75% +/- 7%, respectively. These changes were not significantly different than control rates. In contrast, the increasing concentrations of cimetidine caused significant decreases in the hepatic extraction of lidocaine to values of 78% +/- 8%, 63% +/- 14%, and 48% +/- 14% at concentrations of 0.25, 0.50 and 1.25 micrograms/mL, respectively. The hepatic extraction of indocyanine green, 39% +/- 6%, was not affected by the administration of either omeprazole or cimetidine. Thus, in the rat, omeprazole seems to be a less potent inhibitor of cytochrome P-450 than cimetidine.

Animals↗
PubMed1990

The effect of chronic captopril administration on hepatic blood flow of the rat.

The effect of chronic captopril administration on indocyanine green (ICG) clearance and hepatic extraction has been studied in the rat using the intact liver for ICG clearance and the isolated perfused liver for ICG extraction. The captopril was added to the drinking water to give a calculated daily intake from 0-45 mg kg-1. Hepatic clearance of ICG was dose related from 16.5 +/- 2.4 (control) to 7.2 +/- 1.6 mL min-1 kg-1, respectively. The hepatic extraction of ICG was not significantly different (37 +/- 6%) from the control value in groups on 4 and 45 mg kg-1 daily. Since ICG clearance and extraction are dependent on hepatic blood, a change in ICG clearance without a change in the extraction reflects a similar change in the hepatic blood flow. This remained unchanged at daily captopril intakes of 1 and 4 mg kg-1 and decreased when the daily intake was 10 mg kg-1 or higher. If these results in the rat are applicable to man, the chronic administration of therapeutic doses of captopril (0.5-2 mg kg-1) will not affect the hepatic blood flow.

Animals↗
PubMed1990

DBcAMP stimulates vesicle transport and HRP excretion in isolated perfused rat liver.

To clarify the effect of adenosine 3',5'-cyclic monophosphate (cAMP) on the transcytotic vesicle pathway, we measured the biliary excretion of bile acid, phospholipid, and horseradish peroxidase (HRP) in the isolated perfused rat liver (IPRL) with or without infusion of N6,2'-O-dibutyryl-cAMP (DBcAMP). A linear relationship between bile flow and bile acid excretion was observed in both control and DBcAMP-infused livers. DBcAMP increased the y-axis intercept from 1.10 +/- 0.16 to 1.48 +/- 0.19 microliters.min-1.g liver-1 (P less than 0.01) and the slope from 6.5 +/- 1.99 to 10.77 +/- 1.71 microliters/mumol bile acid (P less than 0.01). DBcAMP also increased the biliary excretion of bile acid and phospholipid during a 1.0 mumol/min infusion of taurocholate. When HRP was pulse loaded for 1 min, HRP appeared in bile in early (4-6 min) and late (20-25 min) peaks. DBcAMP markedly increased the late peak of HRP from 0.33 +/- 0.08 to 1.15 +/- 0.32 ng.min-1.g liver-1 (P less than 0.01), a phenomenon blocked by colchicine. An electron-microscopic morphometric analysis indicated that DBcAMP increased both the density and %area of HRP-containing vesicles in the pericanalicular area, compared with controls, 18 min after a 1-min pulse of HRP. DBcAMP had no effect on the uptake rate of HRP in 4-h primary hepatocyte cultures but stimulated biliary excretion of HRP when preloaded in the IPRL. These findings indicate that cAMP regulates excretory function in part by stimulating the microtubule-dependent transcytotic vesicle transport system.

Animals↗
PubMed1989

The effect of PGE2 on hepatic blood flow and bile indocyanin green in the rat.

The effect of Prostaglandin E2 (PGE2) on hepatic blood flow and bile excretion has been only partially investigated. We studied in the rat the effect of PGE2 on indocyanine green (ICG) clearance, bile flow and ICG recovery in the bile. PGE2 administered to rats at a rate of 2 micrograms/kg/min had no effect on ICG clearance as compared to vehicle-treated rats (14.6 +/- 2.5 Vs, 16.9 +/- 2.5 ml/min/kg) and on bile flow (1.23 +/- 0.15 Vs. 1.24 +/- 0.11 microliters/min/gm liver). However, ICG excretion in bile was significantly increased as compared to a vehicle-treated group, 0.48 +/- 0.09 and 0.25 +/- 0.02 micrograms/microliters bile, respectively (P less than 0.005). This effect of PGE2 on ICG recovery in bile was found to be dose-dependent, and when PGE2 was administered at a rate of 1 microgram/kg/min, bile ICG decreased to 0.33 +/- 0.10 microgram/microliter bile. The effect of PGE2 on bile ICG is not due to an increased extraction of ICG by the liver since using the isolated perfused rat liver, the mean ICG extraction rate over a 20 minute period, with and without PGE2 infusion, was very similar, 33 +/- 3.5 and 37 +/- 6.2 percent, respectively. The lack of effect of PGE2 on ICG clearance and extraction and on bile flow, with an increase in biliary excretion of ICG, suggests a decreased hepatic storage of ICG induced by PGE2 possibly due to an accelerated rate of ICG excretion from the hepatocytes to the bile canaliculi.

Animals↗
PubMed1988

The role of short-term multilumen duodenojejunal manometry in patients with intestinal motor dysfunction.

Short-term duodenojejunal manometry, using a multilumen perfused tube, was performed in 12 patients with symptoms of motor dysfunction, 6 patients with irritable bowel syndrome and predominant diarrhea and 6 patients with chronic constipation. Ten healthy individuals served as controls. The durations, in minutes, of the various phases of the migratory motility complex in the three groups were: phase I: 24.4 +/- 22.1, 26.9 +/- 17.3, and 27.2 +/- 18.5; phase II: 86.7 +/- 25.2, 132 +/- 93, and 73.1 +/- 40.8, and those of phase III: 6 +/- 2.5, 6.8 +/- 5, and 6.4 +/- 1.7, respectively. The differences between patients and controls were not statistically significant. Variables of contractions of phase III in the different groups were: frequency (per minute): 10.9 +/- 0.8, 10.7 +/- 0.4, and 11.3 +/- 0.4; Summation of amplitudes per minute: 205.2 +/- 55.7, 288 +/- 57.9, and 337.8 +/- 76.5; Mean amplitude (mm Hg): 19.1 +/- 4.2, 28.6 +/- 5, and 33.5 +/- 7.1, respectively. Results in the patient groups were not significantly different from controls. Short-term duodenojejunal manometry was normal in patients with irritable bowel syndrome and in those with chronic constipation.

Adult↗
PubMedDate not supplied

Double-blind controlled trial of flumazenil in patients who underwent upper gastrointestinal endoscopy.

The antisedative effect of flumazenil, a benzodiazepine antagonist, was studied in a double-blind placebo controlled trial in 61 patients who underwent upper gastrointestinal endoscopy and sedation with benzodiazepines. The efficacy of flumazenil in reversing the effect of both benzodiazepines, diazepam and midazolam, was significantly higher than placebo (p less than 0.0001). The effect of flumazenil was prompt and was clearly noticed at the first assessment, 5 min after its administration. In none of the patients was a relapse of the sedative effect of the benzodiazepines noticed. The administration of flumazenil was free of major side effects. Flumazenil administration permits an earlier discharge of patients following endoscopy. Its availability in the endoscopy suite may improve the outcome of serious but rare side effects related to benzodiazepines.

Anesthesia, Intravenous↗