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Biomedical subjects

P D Webster

Publications and source records attributed to P D Webster.

At least 37 records · Page 2Linked to original sources

Effect of hormones on pancreatic macromolecular transport.

The role of subcellular organelles in the synthesis, transport, and secretion of pancreatic digestive proteins has been well documented. This study was designed to examine effects of pentagastrin, secretin, and acute and chronic administration of cholecystokinin-pancreozymin (CCK-PZ) on pancreatic macromolecular transport and secretion. Pooled rat pancreas slices were pulse-labeled with L-[14-C]phenylalanine and migration of 14-C-labeled proteins studied by "chase" incubation for 15, 30, 60, and 120 min. After in vitro incubation of control and drug-treated pancreatic slices, subcellular particles were isolated by differential centrifugation; Specific activity of radioactive labeled proteins was determined in subcellular fractions involved in transport and secretion of digestive proteins. These studies indicate that pentagastrin and acute and chronic stimulation with CCK-PZ did not alter the rate of transport of labeled proteins from ribosomes to the zymogen granules. Pentagastrin and CCK-PZ stimulated secretion of labeled proteins from the zymogen granules into the medium in the concentrations used as evidenced by significant increase in the amount of labeled proteins in the medium and significant decrease in the specific activity of the zymogen granule fractions after 60- and 120-min periods of incubation. Secretin did not alter the rate of transport or secretion of the pulse-labeled proteins.

Animals↗

Protein synthesis in pancreas of fasted pigeons.

The regulation of protein synthesis in the pigeon has been studied by comparing the capability of cell-free amino acid incorporating systems of membrane-bound and membrane-free polysomes prepared from fasted and fed birds. New methods were developed for isolating polysomes since techniques used for other tissues did not provide quantitative recovery of polysomal RNA. The sucrose gradient profile of polysomes from pigeon pancreas showed a predominance of trisome species. Although initiation factors are present on polysomes, it was found that polysomes in cell-free systems would not initiate protein synthesis without exogenous initiation factors. This suggested the presence of an inhibitor or regulator of protein synthesis. These studies show that fasting resulted in: (a) decreased amounts of polysomes; (b) disaggregation of polysomes to monosomes; (c) decreased capability of polysomes to synthesize nascent peptides and to initiate additional synthesis, apparently not related to concentration of initiation factors.

Amino Acids↗

Hormonal control of pancreatic growth.

Investigations have outlined pancreatic secretory and synthetic responses to gastrointestinal hormones. However, there is little information concerning hormonal influences on pancreatic growth. These studies were designed to examine effects of chronic administration of bethanechol and cholecystokinin-pancreozymin (CCK-PZ) on the pancreas. Male albino rats were given saline, bethanechol, 6 mg/kg, or CCK-PZ, 20 U/kg, intraperitoneally twice daily and killed after 5 days. The following changes were studied; pancreatic weight; RNA, DNA, and protein content; and [(14)C]thymidine incorporation into DNA. Bethanechol administration was associated with a 20% increase in pancreatic weight and a 33% increase in mg protein/100 mug DNA. In bethanechol-treated groups, amounts of DNA/gram body weight and incorporation of [(14)C]thymidine into DNA were similar to controls. CCK-PZ administration was associated with a 71% increase in pancreatic weight and a 38% increase in mg protein/100 mug DNA. In CCK-PZ-treated groups, amounts of DNA/gram body weight were increased by 42% and [(14)C]thymidine incorporation into DNA was increased by 185%. These studies indicate that bethanechol administration was associated with increases in pancreatic cell mass (hypertrophy). CCK-PZ administration was associated with increases in cell mass and cell numbers (hypertrophy and hyperplasia). This information suggests the importance of CCK-PZ in maintaining pancreatic functional integrity. Although bethanechol and CCK-PZ elicit similar secretory responses, their mode of action on the cell, at least as far as growth influences are concerned, appears to be different.

Animals↗

Effects of fasting and feeding on protein synthesis by the rat pancreas.

These experiments were designed to determine whether fasting and feeding were associated with differing rates of protein synthesis in the rat pancreas. It has been established that feeding, acetylcholine, or cholecystokinin-pancreozymin administration was associated with enhanced rates of digestive enzyme secretion; however, the literature is unclear as to effects of such stimulation on enzyme synthesis. Rats fed ad lib. or fasted 24, 48, or 72 hr were used for this study. Pancreases were removed and incubated in tissue culture medium with l-phenylalanine-(14)C, and incorporation into TCA-insoluble material as well as purified amylase was measured. Compared with fed controls, fasting 24, 48, and 72 hr was associated with 29%, 39%, and 35% decreases in incorporation of l-phenylalanine-(14)C into protein. Decreases of similar magnitudes were apparent whether the data were expressed in terms of protein or DNA. Pancreatic amylase isolated from rats fasted 48 hr contained 57% fewer counts of l-phenylalanine-(14)C than amylase isolated from fed rats. Moreover, rats fasted for 24 hr and given bethanechol chloride incorporated greater amounts of l-phenylalanine-(14)C into protein than fasted controls. Studies were performed to exclude changes in pool size of precursor (l-phenylalanine-(14)C) or product (amylase) in accounting for decreases associated with fasting. These studies demonstrate that fasting was associated with decreased rates of pancreatic amylase and protein synthesis in rats.

Amylases↗