The Effect of Ethionine on the Energy-Producing Metabolism in the Rat Pancreas - II. Alterations of Tissue Levels of Adenine Nucleotides, Pyridine Nucleotides, and Glycolytic Metabolites[*]

Abstract

1) The effect of four different doses of d,l-ethionine (0.05 mg, 0.25 mg, 0.5 mg, and 1 mg per g body weight) upon pancreatic tissue levels of ATP, ADP, AMP, NAD, NADP and glycolytic metabolites five hours after intraperitoneal application was investigated in female rats. Doses of 0.25 mg to 1 mg resulted in a similar, significant decrease in level of adenine and pyridine nucleotides and of most substrates measured. The content of lactate was increased, as was the lactate/pyruvate ratio. These effects were also present after a dose of 0.05 mg/kg body weight, but were far less marked. This indicates a saturation of the mechanism responsible for the deficit of nucleotides when the dosage exceeds 0.25 mg/gm body weight.

2) 1 mg ethionine/gm body weight induced the same alterations even after two hours. They were still present twelve hours after administration.

3) In two experiments 0.05 mg and 0.25 mg/gm body weight of ethionine were given intraperitoneally once daily over a period of four days; on the fourth day the same metabolic alterations were found in the pancreas which had been seen five hours after application of 0.25 mg-1 mg/gm body weight.

4) The reduction of the tissue content of ATP to about 50% of the control level is considered to be the main cause of a disturbance in the intracellular enzyme transport, leading to an accumulation of enzyme protein in the cells. However, it cannot be the sole cause, either of this phenomenon or of the progressive destruction of the cell, because these phenomena are dependent on the applied dose of ethionine. On the contrary the metabolic alterations are not dose dependent above a certain saturating level of the toxic agent.

Key words

d,l - Ethionine - Pancreas - Adenine Nucleotides - Pyridine Nucleotides - Glycolytic Metabolites

1 This study was supported by the Deutsche Forschungsgemeinschaft, grant GO 118/7

1 This study was supported by the Deutsche Forschungsgemeinschaft, grant GO 118/7