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Biomedical subjects

S K Roberts

Publications and source records attributed to S K Roberts.

26 records · Page 2Linked to original sources
PubMed1993

Regulation of bicarbonate-dependent ductular bile secretion assessed by lumenal micropuncture of isolated rodent intrahepatic bile ducts.

While intrahepatic bile duct epithelial cells secrete bile through transport of ions and water, the physiological mechanisms regulating ductular bile secretion are obscure, in part because of the lack of suitable experimental models. We report here the successful micropuncture of the lumen of isolated intrahepatic bile ducts and direct measurements of ductular ion secretion. Intact, polarized bile duct units (BDUs) were isolated from livers of normal rats by enzymatic digestion and microdissection. BDUs were cultured and mounted on a microscope in bicarbonate-containing buffer, and the lumens were microinjected with 2',7'-bis(2-carboxyethyl)-5-(and -6)carboxyfluorescein (BCECF)-dextran. Lumenal pH was measured by ratio imaging of BCECF fluorescence using digitized video fluorescent microscopy. After 36 hr in culture, the ends of BDUs sealed, forming closed compartments. After lumenal microinjection of BCECF-dextran, fluorescence was stable at the pH-insensitive wavelength, indicating no dye leakage. Serial changes in pH of extralumenal buffers containing pH-gradient collapsing ionophores allowed us to establish reliable standard curves relating fluorescence ratio to lumenal pH (r = 0.99; P < 0.001). By this approach, the basal pH inside the lumen of BDUs was 7.87 +/- 0.08 units (n = 9), 0.47 unit higher (P < 0.001) than the bathing buffer pH. Addition of 100 microM forskolin increased (P = 0.02) the lumenal pH from 7.78 +/- 0.06 to 7.97 +/- 0.06 units (n = 5); the forskolin effect was completely abolished by incubation of BDUs in HCO3-/CO2-free buffer. Moreover, forskolin caused a 50-fold increase in cAMP levels in BDUs. The observations are consistent with cAMP-dependent, active lumenal HCO3- secretion by BDUs. Furthermore, they demonstrate the suitability of the BDU model for studying regulatory and mechanistic aspects of ductular bile secretion.

Analysis of Variance↗
PubMed1993

Modulation of uptake of heme by rat small intestinal mucosa in iron deficiency.

Although body iron status modulates whole body retention of heme derived iron, it is not known with certainty whether modulation occurs by regulation of mucosal uptake of heme. In vivo uptake from perfused intestine of heme labeled with 14C in the porphyrin ring was studied in groups of rats of differing iron status ranging from fully replete to markedly iron deficient. Heme extraction from infusate and mucosal heme uptake were significantly different between test groups (P < 0.005 and 0.001, respectively). Marked iron deficiency induced a 4.8-fold rise in heme extraction relative to iron-replete animals; rats with latent iron deficiency showed a smaller but still significant rise. Heme extraction correlated negatively with indicators of iron status: hemoglobin (r = -0.76, P < 0.001) and serum iron (r = -0.56, P < 0.05). The specific binding of [14C]heme to purified brush borders from iron-replete and iron-deficient rats was 1.4-fold higher in deficient rats when expressed per milligram of protein (P = 0.046) and 3.3-fold higher when expressed relative to alkaline phosphatase activity (P = 0.014). Thus mucosal uptake of heme in iron deficiency is increased because of an increase in its binding to the brush border.

Animals↗
PubMed1978

Glucose, glycine and diglycine in test meals at stimuli to a duodenal osmoreceptor slowing gastric emptying.

1. Five subjects took 210 test meals of 750 ml. water containing 30--300 m-molal glucose or glycine, or 15--150 m-molal diglycine, or plain water. 2. The greater the concentration of solute, the greater was the volume of original meal recovered from the stomach after a fixed time. 3. On a molal basis glucose was half as effective as diglycine in slowing gastric emptying. This was consistent with the osmoreceptor being exposed to the diglycine after it had been split by the hydrolase of the cytosol of enterocytes (the absorbing cells of the small intestine). 4. The slowing of gastric emptying (ml./mole.1.) was about 10% greater for glycine than it was for glucose. There was apparently a threshold concentration below which glycine did not slow gastric emptying. 5. It was proposed that the response of the doudenal osmoreceptor might depend upon shrinking and swelling of the lateral intercellular space around the enterocytes.

Chemoreceptor Cells↗
PubMed1974

Actions of glucose and potassium chloride on osmoreceptors slowing gastric emptying.

1. Five subjects were given 373 test meals of 750 ml. water containing a range of concentrations of glucose or potassium chloride.2. The greater the concentration of solute in the meals, the greater was the volume of the test meal recovered from the stomach after a fixed time.3. When the concentrations of the solutes were expressed as m-osmole/l. corrected by osmotic coefficients based on vapour pressures at 37 degrees C, glucose and potassium chloride were indistinguishable in slowing gastric emptying.4. These results are consistent with the regulation of gastric emptying by a duodenal receptor responding to osmotic pressure.5. Potassium chloride was more nauseating than glucose on an osmolar basis.

Duodenum↗