Abstract
The effect of oxygen free radicals generated by xanthine-xanthine oxidase system and hydrogen peroxide were investigated on cardiac muscarinic cholinergic receptors. We have used highly enriched sarcolemmal preparations isolated from canine myocardium. Exposure of the sarcolemma to oxygen free radicals by xanthine-xanthine oxidase system resulted in a significant (P < 0.05) decrease of B max of ( 3H)-QNB (4.66 ± 0.51 to 2.68 ± 0.22 pmoles/mg protein). Addition of superoxide dismutase (SOD) and catalase (10 μg/ml) resulted in a significant reversal of B max value to 3.72 ± 0.39 pmoles per mg protein (p < 0.05). However, the affinity constants of dissociation (K D) were not altered appreciably with the exposure to oxygen free radicals with or without scavengers. Hydrogen peroxide significantly depressed 3H-QNB binding to the receptors in a dose-dependent manner in a concentration range between 4.41 mM − 441 mM. This depression was completely inhibited by 10 μg/ml catalase. The study demonstrates that the oxygen free radical species are capable of disrupting ( 3H)-QNB binding to the cardiac muscarinic receptors.
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