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Biomedical subjects

H Petersen

Publications and source records attributed to H Petersen.

At least 145 records · Page 8Linked to original sources

Effects of gastrointestinal polypeptides on hormone content of endocrine pancreas in the rat.

Although trophic actions of gastrointestinal peptides on exocrine pancreas have been shown, little is known regarding their effects in endocrine pancreas. Therefore, we measured the contents of somatostatin-like immunoreactivity (SLI), insulin and glucagon, in pancreatic extracts from rats that had been treated three times a day for 10 days with saline; 1 microgram/kg caerulein; 5, 25, and 100 microgram/kg secretin; 1 microgram/kg caerulein plus 5, 25, and 100 microgram/kg secretin; 25 microgram/kg pancreatic polypeptide; 15 microgram/kg glicentin; or 15 microgram/kg gastric-inhibitory polypeptide. Pancreatic SLI content was significantly increased in rats treated with glicentin and caerulein plus secretin at the two higher doses. No difference was noted between the control and the caerulein plus 100 microgram/kg secretin groups in delta-cell number per islet when examined by the immunoperoxidase technique. These data suggest that because of their effect on SLI content gastrointestinal polypeptides may modulate pancreatic endocrine function.

Animals↗

Pancreatic secretion in rats after chronic treatment with secretin plus caerulein.

Rats were given subcutaneous injections of secretin (12.5 microgram kg-1) plus caerulein (0.5 microgram kg-1) in a depot carrier or depot carrier alone every 8 hr for 10 days. Basal pancreatic secretion and responses to secretin and cholecystokinin were then studied while the rats were under urethane anesthesia. In the treated animals, basal secretion of fluid was more than six times greater, basal bicarbonate output more than three times greater, and and basal protein output more than two times greater than in the control rats (P less than 0.01 for each). After subtracting basal values and normalizing for body weight, the treated group means were statistically significantly greater than those of the control for: maximal bicarbonate output (1.81 times control) to secretin; and maximal outputs to cholecystokinin of volume (2.46 times control), bicarbonate (2.69 times control), and protein (2.28 times control). The mean pancreatic weight per kilogram of body weight in the treated group was 1.65 times (P less than 0.01) that of the control group. When normalized for pancreatic weight (basal values subtracted), the increse in maximal protein output (1.37 times control) to cholecystokinin was still statistically significant (P less than 0.05). We conclude that chronic treatment with secretin plus caerulein exerts a trophic effect on the pancreas associated with increased maximal protein output to cholecystokinin and increased maximal bicarbonate output to secretin.

Animals↗

Three-dimensional molecular illustrations I: Isoelectron density contours and isoelectrostatic energy contours.

A method of depicting dimensional illustrations of molecules in vacuo that are sensitive to small electronic perturbations was attempted. This method would be useful in determining the effects of either perturbing groups from other molecules or changes produced by the addition or modification of an existing atom or chemical group on the same molecule. Isoelectron density contours for small molecules such as benzene, ammonia, and formaldehyde were first considered using the CNDO/2 molecular approximation method and then extended to the use of deorthogonalized CNDO/2 eigenvectors. These methods were similar in molecular projections but insensitive to electronic alterations. Therefore, the electrostatic potential energy was considered in developing contour surfaces of several of the molecules studied. In this case, acute and visually discernible changes were evidenced by electron exchange in the three-dimensional illustration of formaldehyde. The effect on the two-dimensional contour map of ammonia was strikingly altered by the addition of a proton, further substantiating the sensitivity of electrostatic contours to perturbing influences. These methods are considered and amplified in this report.

Ammonia↗

Three-dimensional molecular illustrations II: Isoelectrostatic energy contour spheres of influence applied to narcotic molecules.

A computer-generated method using quantum mechanics was applied to the calculation and subsequent plotting of nonperspective three-dimensional illustrations of molecules in vacuo. The purpose was to generate isoelectrostatic energy contour spheres for larger molecules and current drugs. The molecules chosen, morphine, meperidine, and alphaprodine, possess similar pharmacological properties. Minor configurational manipulation of meperidine and alphaprodine molecules was made to approximate the spatial configuration of the rigid morphine molecule so that direct comparisons were possible. Common areas of reactivity, potential energy minima, net atomic charges, spatial regions, and near neighbor influences are considered.

Computers↗

Stimulation of gastric acid secretion by dimaprit in unanesthetized rats.

In unanesthetized rats, dimaprit and histamine given by intravenous infusion were about equipotent in stimulating gastric acid secretion. The maximal rate of acid secretion in response to dimaprit was significantly greater than to histamine but not significantly different from the response to pentagastrin.

Animals↗

Effect of chronic pentagastrin, cholecystokinin, and secretin on pancreas of rats.

Pentagastrin (1.5 mg/kg), 20% pure natural cholecystokinin (CCK, 37.5 Ivy dog U/kg) or secretin (25 microgram/kg) was given in a depot carrier subcutaneously to rats 3 times daily for 15 days. The dose of CCK and secretin was submaximal for pancreatic secretion, whereas the dose of pentagastrin was supramaximal for gastric acid secretion. The pancreatic wet weight increased by 12% (P less than 0.01) in the rats treated with pentagastrin, 57% (P less than 0.001) in those treated with CCK, and 9% (P less than 0.01) in those treated with secretin. In CCK-treated rats, the maximal protein and bicarbonate outputs in response to cholecystokinin increased proportionately to the increase in pancreatic weight, but maximal bicarbonate and protein outputs in response to secretin were unaltered. The secretin-treated rats showed a lowered basal secretion of bicarbonate and a lowered sensitivity to secretin stimulation, but the maximal bicarbonate and protein outputs to secretin and CCK were unchanged. Treatment with pentagastrin produced no significant changes in pancreatic responses to secretin or CCK. We conclude that 1) the increase in pancreatic weight produced by repeated injections of cholecystokinin was accompanied by proportional increase in functional capacity as reflected by the increased maximal bicarbonate and protein outputs in response to cholecystokinin, and 2) repeated administration of secretin decreased the sensitivity of the pancreas to secretin without altering maximal bicarbonate response.

Animals↗

Interaction of caerulein and secretin on pancreatic size and composition in rat.

Rats were given injections of caerulein, secretin, or a combination of these two peptides subcutaneously 3 times daily for 5, 10, or 15 days. Caerulein produced significant dose- and time-dependent increases in pancreatic weight and content of DNA, RNA, protein, amylase, and trypsinogen. Secretin produced significant increases in pancreatic weight and content of RNA and lipase after 15 days of treatment. After only 5 days of treatment with a combination of secretin plus caerulein, pancreatic weight and content of RNA and protein more than doubled, and trypsinogen content increased more than fivefold. Comparing the averages across the 5-, 10-, and 15-day values, increases in weight, protein, and trypsinogen with the combination of secretin plus caerulein were significantly greater than the sum of the effects of the peptides given singly. Using increase in DNA content as an index of hyperplasia and increases in the ratios of pancreatic weight, RNA content, and protein content to DNA content as indices of hypertrophy, we concluded that caerulein produced both hyperplasia and hypertrophy of rat pancreatic acinar cells. Secretin markedly augmented the hypertrophic action of caerulein but did not alter its hyperplastic action.

Amylases↗

Comparison of juice obtained during duodenal aspiration and cannulation of the main pancreatic duct after stimulation with exogenous secretin in man.

The exocrine pancreatic secretion obtained by endoscopic cannulation was compared with that obtained by a conventional duodenal tube after exogenous secretin. The flow rate, bicarbonate output, and amylase output in response to secretin was larger during duodenal aspiration than when collecting during endoscopic cannulation. The majority of samples collected from the duodenum contained bile, whereas those from the pancreatic duct were, with few exceptions, colourless. In all patients the bicarbonate concentration was lower in the duodenal aspirate than in the pancreatic juice. In 5 of the 7 patients, however, the concentration of amylase was higher in the duodenal aspirate than in juice collected by endoscopic cannulation. In these patients the quantitative difference found could not therefore solely be explained by non-quantitative collection of juice from the pancreatic duct and/or contamination of bile, intestinal juice, and gastric juice in the duodenum. Augmentation of the response to secretin by the presence of bile and pancreatic juice in the duodenum and inhibition by the endoscopic cannulation of the pancreatic duct are discussed as alternative explanations.

Adult↗