Inhibition Of Pancreatic Secretion Research Articles

Influence of bicarbonate-CO 2 - and glycodiazine buffer on the secretion of the isolated cat's pancreas.

The isolated cat pancreas was perfused with solutions containing different concentrations of bicarbonate- or glycodiazine buffer. The concentrations of the different buffer components were varied in order to determine the rate-limiting component. Considering also earlier findings with sulfamerazine buffer a model is proposed where a H+/OH− ion separation takes place at the luminal cell border of the exocrine pancreas cells. Undissociated acid as well as buffer anions neutralize the H+ resp. the OH− ions thereby promoting the buffer secretion. The rate-limitation with each buffer component seems to be dependent on its concentration and permeation properties. The inhibition of pancreatic secretion by the undissociated glycodiazine is presumably caused by its effects on the mitochondrial energy production.

The origin and secretion of pancreatic juice bicarbonate.

1. The rate of secretion from a saline-perfused preparation of the cat's pancreas is directly proportional to the perfusate bicarbonate concentration. When all bicarbonate is omitted, secretion completely or almost completely ceases.2. Incorporation of [(14)C]bicarbonate into the perfusion fluid results in its prompt appearance in the juice. The radioactive label is concentrated four to five times in the juice just as the total juice bicarbonate is four to five times greater than perfusate bicarbonate.3. These two observations suggest that about 95% of pancreatic juice bicarbonate is derived from perfusate (plasma) bicarbonate.4. The inhibition of pancreatic secretion from the perfused gland by acetazolamide is similar to that observed in the intact animal.5. There is a fall in pH and rise in P(CO2) in the perfusion fluid leaving the gland which is greater during secretion than at rest.6. It is therefore suggested that during secretion, hydrogen ions pass from the gland into the perfusate (plasma), thus increasing the production of carbon dioxide from circulating bicarbonate. This carbon dioxide diffuses into the cell, is rehydrated (partly under the influence of carbonic anhydrase) and finally is secreted, thus establishing the necessary gradient for the continued diffusion of carbon dioxide into the cell.

Inhibitory effect of new anticholinergics on the basal and secretin-stimulated pancreatic secretion in patients with and without pancreatic disease: therapeutic and theoretic implications.

1. The anticholinergic piperidyl drugs are more potent inhibitors of pancreatic secretion than atropine or the Banthine compounds. Greater suppression of secretion can be obtained with them without the undesirable side reactions noted with the atropine-Banthine drugs. Therefore, these anticholinergics should be superior to the latter in the therapy of pancreatic inflammation. Preliminary clinical experiences would indicate a worthiness for further therapeutic scrutiny. 2. The previously reported pharmacologic observation of preferential anticholinergic action appears to be substantiated by the experimental findings. 3. The inhibition of the secretin responses to ranges up to 95 per cent has not been previously noted with anticholinergics either in man or in the experimental animal. This finding casts doubt upon the present physiologic concept of the regulation of pancreatic secretion by independent mechanisms—i.e., the hormonal and nervous—and favors rather the Thomas-Pavlovian hypothesis of interdependence. 4. Analysis of the alteration of flow-bicarbonate relationships following these anticholinergics indicate a persistence of bicarbonate concentration at falling rates of secretion. This observation supported by the changes in electrolyte secretion after Diamox and after ACTH and the adrenal steroids, and by those changes recorded in diseased states of the pancreas, adds further evidence to the hypothesis of ductular function within the pancreas.

Inhibition of pancreatic secretion by the carbonic anhydrase inhibitor 2-acetylamino-1,3,4-thiadiazole-5-sulfonamide, diamox (#6063).

Inhibition of pancreatic secretion by the carbonic anhydrase inhibitor 2-acetylamino-1,3,4-thiadiazole-5-sulfonamide, diamox (#6063).

Inhibition of pancreatic secretion by the carbonic anhydrase inhibitor, 2-acetylamino-1,3,4, thiadiazole-5-sulfonamide (compound No. 6063).

SummaryIntravenous injection of 2-acetylamino −1,3,4 - thiadiazole-5-sulfonamide (compound No. 6063) in pancreatic fistula dogs results in a marked reduction in the volume output and the bicarbonate concentration of pancreatic secretion following stimulation with secretin. Since this compound is a potent inhibitor of carbonic anhydrase activity in vivo, it is likely that this reduction in secretory activity results from a similar inhibition of the carbonic anhydrase present in the pancreas. This supports the view that this enzyme plays a dominant role in bicarbonate formation by this gland.Statistical analyses of the concentration-volume data will be published later in a detailed report of this work.

THE INDUCTION OF PANCREATIC ACTIVITY BY THE REMOVAL OF THE ADRENALS

We reported before the Association of American Physicians in Washington, May, 1909,1the results of our work on the relation of certain ductless glands to the pancreas, and we there offered among other conclusions, the following: The inhibition of pancreatic secretion by adrenalin is independent of systemic blood-pressure, as shown by its persistence when the blood-pressure is much below normal and by other evidence. The inhibition by extracts of pituitary and suprarenal bodies also occurs when the pancreas is stimulated by its normal excitant, hydrochloric acid in the duodenum. The evidence now at hand indicates that the suprarenal glands exercise an inhibitory power on the pancreas, and that on the removal of this influence by ablation the pancreas secretes more actively. The agonal period of life (in the sense described) is generally accompanied by an exacerbation of the normal rate of pancreatic