Effects of carbamylcholine and pyridostigmine on mitochondrial-bound hexokinase in skeletal muscle and heart.

We show here that carbamylcholine (acetylcholine agonist) or pyridostigmine (acetylcholinesterase inhibitor), drugs which are widely used in medical treatments, exerted a rapid reduction in mitochondrial-bound hexokinase. This reduction was inversely proportional to the changes in glucose-6-phosphate levels in skeletal and heart muscle. Increased concentration of acetylcholine, occurring in various diseases or induced by acetylcholinesterase inhibitors, was reported to cause deterioration of mitochondrial function, resulting in heart and muscle damage. The present experiments suggest that the reduction in mitochondrial-bound hexokinase, which is closely linked to intramitochondrial oxidative metabolism, may play an important role in the mechanism which leads to tissue damage.