Exocytosis in mammalian cells. II. Topography of ferritin-concanavalin A conjugate and ruthenium red binding sites on the luminal surface of pancreatic acinar cells.
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Biomedical subjects
Publications and source records attributed to A R Beaudoin.
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The developmental origin of arsenate-induced renal agenesis was investigated. Pregnant Wistar rats were each injected once ip with 45 mg/kg sodium arsenate at day 10 (sperm day = day 0). Pregnancy was terminated at various times following injection and the embryos recovered and serially sectioned. Renal agenesis resulted when the mesonephric duct failded to give rise to a ureteric bud with subsequent failure of induction of the metanephric blastema. The underlying defect was retardation in growth of the mesonephric duct, first observed 48 hours after arsenate injection. A shortened mesonephric duct also resulted in a failure of the mesonephros to attain normal size and in the male resulted in absence of the ductus deferens, seminal vesicle a variable portion of the epididymis. Due to the intimate association of the mesonephric and growing paramesonephric ducts, a shortened mesonephric duct resulted in a shortened paramesonephric duct with resultant lack of a uterine horn.
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An acyl-CoA-L-alpha-glycerophosphate acyltransferase system has been found in the fat body of the locust Schistocerca gregaria (Forskäl). After homogenization and differential centrifugation the enzyme system has been localized in two distinct particulate fractions. In both fractions phosphatidic acid was the main reaction product. The 10 000 g -30 000 g particulate fraction was further studied. The enzyme system is very sensitive to pH and Mg2+ concentration. An apparent Km of 0.3-0.5 mM for glycerophosphate was measured. The substrate concentration curve for palmitoyl-CoA is influenced by the protein concentration in the assay medium. This effect would partly explain the non-lineariy of the acylation reactions with respect to enzyme concentration. These observations are correlated with physiological phenomena.
Pancreatic enzyme secretion induced by urecholine or cholecystokinin-pancreozymin (CCK-PZ) is inhibited by tetracaine. If the pancreatic tissue is preincubated with tetracaine then washed out, the subsequent response to CCK-PZ is not affected while that to urecholine is impaired. In contrast with atropine, tetracaine loses its inhibitory potency once secretion has been initiated by urecholine before the addition of the local anaesthetic. Calcium efflux studies have shown that addition of tetracaine in vitro is associated with release of calcium in the incubation medium. This effect on calcium efflux might explain partly the inhibitory action of the drug.
These experiments were performed to evaluate the effects of cytochalasin B on pancreatic enzyme secretion and thus perhaps establish a role for microfilaments in the exocytosis process. The alkaloid at a concentration of 1 microgram/ml (2micron) inhibits amylase secretion induced by urecholine or cholecystokinin-pancreozymin (CCK-PZ) but does not modify that induced by dibutyryl cyclic AMP. The inhibitory effect of the drug is reversible after a 30-min washing out period. It does not affect O2 consumption, basal calcium efflux, or efflux caused by CCK-PZ. Amino acid accumulation in the tissue and their incorporation into proteins are not modified. It is suggested that cytochalasin B inhibits pancreatic enzyme secretion, probably through an effect on the microfilament system.
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The relationship between fatty acid composition and phospholipid pattern has been studied in Escherichia coli auxotrophs for unsaturated fatty acids. 1. The presence of a regulatory mechanism which enables the organism to maintain a given fluidity of the lipids has been corroborated using exogenous fatty acids which cause dramatic changes in fatty acid composition. 2. The fatty composition of phosphatidic acid is different from that of the other classes of phospholipids. 3. Changes in fatty acid composition are concomittant with the alteration of the phospholipid pattern. The ratio of phosphatidylglycerol to diphosphatidylglycerol is particularly sensitive to the physical characteristics of the exogenous unsaturated fatty acid. The relative increase in diphosphatidylglycerol is associated with membrane alterations.
The teratogen 2-amino-1,3,4-thiadiazole (ATDA) is an antagonist of nicotinamide, and may act by interfering with the synthesis or utilization of the coenzyme nicotinamide adenine dinucleotide (NAD). Several compounds that can be converted to NAD were tested as antiteratogens against ATDA. At day 11 of gestation (sperm day = day 0) pregnant Wistar-derived rats were given single ip injections of ATDA (100 mg/kg), or ATDA immediately followed by the suspected antiteratogen ip or by gavage, or the antiteratogen alone. Compounds tested were NAD, nicotinamide, nicotinic acid, quinolinic acid, kynurenine sulfate, and L-tryptophan, in doses of 10-200 mg per animal. At autopsy (day 20) fetuses were recovered and examined. It was found that each antiteratogen significantly reduced the frequency of ATDA-induced resorptions and malformations. At certain doses each anteteratogen gave complete protection against ATDA-induced malformations in some, but not all, litters. These results support the hypothesis that ADTA interferes with the synthesis or utilization of NAD and suggest that substances converted to NAD act as antiteratogens against ATDA.
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