THE INHIBITORY EFFECT OF PAPAVERINE ON RESPIRATION-DEPENDENT CONTRACTURE OF GUINEA PIG TAENIA COLI IN HIGH-K MEDIUM. II. INHIBITION OF MITOCHONDRIAL RESPIRATION

Abstract

To elucidate the inhibitory action of papaverine (Pap) on the highly respiration-dependent contracture of guinea pig tenia coli in 40 mM K (40-K) medium, the effects of Pap and rotenone (Rot) on the respiration of mitochondria (Mt) were examined using guinea pig tenia coli, rat liver and pigeon heart. The addition of Pap to tenia coli Mt at a concentration which inhibits the muscle contracture rapidly inhibited the aerobic oxidation of glutamate but not succinate. A peak of cytochrome (cyt) br was not observed in the Mt which were treated with Pap and contained glutamate. These results were confirmed and extended to rat liver Mt. Both the tenia coli Mt and the heart Mt oxidized NADH when added as a substrate. Pap (10-5 - 10-4 M) inhibited the oxidation of NADH by both Mt to almost the same degree as it inhibited the respiration of the muscle strip in 40-K medium. Raising the NADH concentration did not antagonize inhibition by Pap. NADH-ferricyanide reaction in both Mt occurred essentially as reported in the electron transport particle of heart Mt. The reduction of ferricyanide was scarcely inhibited by Pap. The effects of Pap and Rot were identical. Pap probably inhibits the electron transport of the mitochondrial respiratory chain between NADH dehydrogenase and coenzyme Q1O (CoQ) on the O2 side of the dehydrogenase, thereby inhibiting the contracture.