Effects of Quinidine on Triacetin Utilizing Activity of Pancreas. ∗

Abstract

Summary

Pancreatic TUA is reversibly inhibited by quinidine and quinine. Quinidine inhibition can be reversed by triacetin to about 70%; however, protection by triacetin could not be demonstrated. Quinidine and related compounds are effective as inhibitors of pancreatic triacetin utilizing activity in the following order: quinine sulfate > quinidine sulfate; quinidine gluconate> quinidine sulfate. To the extent tested, the same relationship holds for wheat germ lipase using triacetin as substrate. In the wheat germ lipase system the K_i for quinidine sulfate = 1 × 10³, and the K_i for quinine sulfate = 5.7 × 10⁴. Heparin inhibits the pancreatic TUA in presence or absence of quinidine. Metals, such as Cu⁺² and Mg⁻² inhibit this system and Cu⁻² increases quinidine inhibition but Mg⁻² does not. Fe⁻³ does not inhibit the system or interfere with quinidine inhibition. EDTA inhibits this system by 70% at a level of 10⁻³ M. This inhibition is partially reversed by Ca⁺² ions which also markedly stimulate TUA activity. EDTA does not greatly influence quinidine inhibition. Cu⁺² inhibition is partially reversed by EDTA in spite of the fact that EDTA is an inhibitor. EDTA reduces the stimulatory effect of Ca⁺². Quinidine inhibition is only slightly lessened by Ca⁺² so that it appears that the site of action of quinidine may not involve a Ca⁺² ion stabilizer.