Dose Response Relationship of Pancreatic Enzyme Stimulants: Pancreozymin and Methacholine

Abstract

Relationship between the dose of the stimulants pancreozymin and methacholine and the secretion of amylase by the pancreas has been studied. The nembutalized dogs were given a continuous intravenous infusion of secretin during the entire course of the experiments and samples of pancreatic juice were collected every 10 minutes for amylase determination. The average minimal dose required for elevation of enzyme output was 0.025 mg and 0.008 µg/kg body weight for pancreozymin and methacholine, respectively. The response to these doses at the start and end of the experimental period were quite similar. Over a wide dosage-range of both methacholine and pancreozymin, the absolute rise in amylase output was a linear function of the logarithm of the dose. Within a small portion of the S-shaped curve obtained by correlating the absolute increase in output with the absolute value of the dose, an apparent linear proportionality existed at low dosage levels. No synergism between pancreozymin and methacholine was found; the combined effect was additive. The gland was practically inexhaustible by continuous stimulation for 20 hours and the enzyme could be made at the rate secreted within the dosage-range of the stimulants used. Practical suggestions have been made for the bioassay of stimulants of pancreatic enzyme output.