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J Sellin

Publications and source records attributed to J Sellin.

9 recordsLinked to original sources

Short-chain fatty acid (SCFA) volume regulation in proximal and distal rabbit colon is different.

SCFAs increase the volume of many different cell types rarely exposed to significant concentrations of these weak electrolytes. SCFAs swell isolated cells from colonic carcinoma cell lines, but the-mechanism(s) of volume regulation in normal colonocytes, which are generally exposed to > 100 mM SCFAs, has not been well characterized. AIMS. To determine the effect of SCFAs on volume regulation in proximal and distal rabbit colonocytes. METHODS. Isolated colonocytes were plated on coverslips and placed in a perfusion apparatus that permitted fluid changes. Cells were continuously monitored by video-microscopy; volume was estimated by measured changes in the radius of individual cells. RESULTS. Distal colonocytes (DC) consistently had a slightly greater basal volume than proximal colonocytes (PC): [14.2 pl/fl:9.8 pl/fl] In HEPES-buffered solutions, an isotonic change to a 90 mM NaCl/50 mM Na propionate solution elicited a significant increase in cell volume within 10 min, but no noticeable regulatory volume decrease over 30 min: V/Vo in DC: 1.29 +/- .09; in PC: 1.25 +/- .05. In HCO3-buffered solutions, 50 mM PROP caused significantly greater cell swelling; in DC: 1.74 +/- .21; in PC: 1.52 +/- .08. In DC both amiloride and EIPA blocked the SCFA-induced increase in cell volume. A hypotonic challenge confirmed that these cells were capable of swelling. In contrast, amiloride did not significantly inhibit SCFA-induced swelling in PC: control, 1.25 +/- .05; amiloride, 1.36 +/- .10. Cell volume increased in PC perfused with an isosmotic 50 mM propionate, Na-free solution: 1.22 +/- .04. CONCLUSIONS. (i) SCFAs induce significant cell swelling, but no regulatory volume decrease, in isolated colonocytes; (ii) HCO3 augments SCFA-induced cell swelling; (iii) volume increase in DC is dependent on Na-H exchange, but in PC appears to be Na-independent. SIGNIFICANCE. There are fundamental differences in how proximal and distal colon respond to isosmotic volume challenge of SCFAs.

Animals↗

Hormonal and pharmacologic regulation of sodium absorption in rabbit cecum in vitro.

The rabbit cecum is a moderately tight epithelium with amiloride-resistant but phenamil-sensitive electrogenic Na absorption. We performed flux and electrical studies under short-circuit conditions in vitro to further characterize the mechanisms of ion transport in cecum in normal and animals pretreated with methylprednisolone (MP) and deoxycorticosterone acetate (DOCA). MP treatment increased Na absorption and decreased tissue conductance. In contrast, DOCA increased Isc but did not significantly alter Na or Cl fluxes. Amiloride analogs with primary specificity for Na channel and Na/H exchanger both inhibited Isc and Na absorption. Ethacrynic acid, but not bumetanide, inhibited Isc. Nystatin and amphotericin B increased Isc. We conclude that: (1) Steroids have a differential effect on cecal ion transport; methylprednisolone increases Na absorption, but DOCA does not. (2) The response to amiloride analogs is different from other electrogenic transport systems, suggesting a distinct mechanism of Na transport in cecum. (3) The effect of ethacrynic acid was unexpected, suggesting an inhibitory response on an alternate transport system. (4) The effects of polyene antibiotics are similar to those found in other tight epithelia. Electrogenic Na absorption in rabbit cecum represents a distinct transport system, significantly different from Na absorptive mechanisms in other segments of the gut.

Amiloride↗

Atrial natriuretic factor and cyclic guanosine monophosphate: ion transport in rat colon in vitro and in vivo.

The role of atrial natriuretic factor receptors in the colon is uncertain. Accordingly, the effects of atrial natriuretic factor in vivo and in vitro were studied. In vivo perfusion of the colon in Sprague-Dawley rats was used to measure Na+, K+, Cl-, and water transport, while atrial natriuretic factor was infused into the jugular vein at 0.5 or 1.0 micrograms.kg-1.min-1. In vitro experiments in Ussing chambers measured short-circuit current and ion fluxes before and after atrial natriuretic factor administration. Because cyclic guanosine monophosphate is thought to be a second messenger for atrial natriuretic factor, short-circuit current was also determined before and after exposure to 8-Br-cyclic guanosine monophosphate. Plasma atrial natriuretic factor (atriopeptin III) levels were determined by radioimmunoassay. The in vivo transport of water, sodium, and chloride and the secretion of potassium were not altered by atrial natriuretic factor infusion. In vitro studies showed no change in Na+ or Cl- transport or change in short-circuit current. Plasma atrial natriuretic factor concentrations increased from 139 +/- 55 pg/mL to 1385 +/- 396 pg/mL during infusion, and urine output increased from 12.6 +/- 0.5 microL/min to 37.4 +/- 2.9 microL/min (P less than 0.05). In contrast, 8-Br-cyclic guanosine monophosphate in vitro caused a significant (P = 0.0004) increase in short-circuit current from 1.2 +/- 0.2 to 2.9 +/- 0.3 microEq.cm-2.h-1.

Animals↗

Evaluation of BW942C, a novel antidiarrheal agent, against enterotoxins of Escherichia coli and Vibrio cholerae.

BW942C, an enkephalin-like pentapeptide with anti-diarrheal activity, was tested against crude toxins of Escherichia coli and Vibrio cholerae in the Y-1 adrenal cell assay, rabbit ileal loop assay, and suckling mouse assay. The effects of BW942C on in vitro ion transport were measured in rabbit ileum mounted in Ussing chambers. In vitro, BW942C decreased basal short-circuit current (2.26 and 3.15 mueq cm-2 h-1 in experimental samples and controls, respectively; n = 7, P less than 0.05) and increased basal net Cl absorption (1.59 and 0.50 mueq cm-2 h-1 in experimental samples and controls, respectively; P less than 0.025). Net Na absorption was also increased, but not significantly. BW942C did not block the secretory response to a maximal dose of purified heat-stable toxin. BW942C directly enhanced intestinal fluid absorption. In the Y-1 adrenal cell assay, 5 mg of BW942C per ml inhibited the cytopathic effect caused by cholera toxin or heat-labile enterotoxin of E. coli. In the rabbit ileal loop assay, E. coli heat-stable toxin, E. coli heat-labile enterotoxin, and cholera toxin were inhibited 35 to 70% by administration of BW942C. With the suckling mouse model, the fluid accumulation caused by E. coli heat-stable toxin was ablated by prior treatment with BW942C. The drug is currently being evaluated in patients with acute secretory diarrhea to determine its effect on clinical symptoms.

Animals↗

Gastric adenocarcinoma following gastric lymphoma. Role of partial gastrectomy.

Gastric adenocarcinoma developed in a 45-year-old man 13 years after he had undergone resection of a gastric lymphoma (large cleaved cell type, diffuse) and two courses of radiation therapy to the upper abdomen to a total dose of 6300 rad. Three factors involved in possibly increasing risk for the second malignancy, namely lymphoma, extensive radiation therapy, and gastric resection, are discussed. Degenerative and premalignant histologic changes occur in the gastric remnant after partial gastrectomy. These contribute to the pathogenesis of adenocarcinoma after surgical therapy of peptic ulcer or other disorders. Periodic endoscopic surveillance and the use of multiple biopsies are important in achieving early diagnosis.

Adenocarcinoma↗

Role of ligandin in transfer of bilirubin from plasma into liver.

Multiple-indicator dilution studies of labeled bilirubin uptake were carried out on isolated perfused rat livers with variable ligandin concentrations (from normal and thyroidectomized animals with and without phenobarbital pretreatment). Ligandin concentrations, measured immunologically, increased 25% after thyroidectomy and approximately doubled after phenobarbital pretreatment but decreased to normal during perfusion in the thyroidectomized nonpretreated group. A distributed two-compartment model was fitted to the dilution data and estimates of influx, efflux, and sequestration coefficients were obtained. Influx and sequestration coefficients did not vary significantly between the groups. Efflux coefficients were significantly smaller (P less than 0.001), and hepatic ligandin concentrations were significantly larger (p less than 0.001) in phenobarbital-treated rats than in other groups. The efflux coefficient varied inversely with ligandin concentration and the volume of distribution in tissue, as perceived from the plasma space, increased in proportion to the concentration of ligandin. The increased net uptake of tracer bilirubin by the liver of phenobarbital-pretreated animals is due to decreased tracer efflux secondary to the increase in intracellular binding of bilirubin by ligandin.

Animals↗