Effect of reduced oxygen intermediates on sarcolemmal muscarinic receptors from canine heart.
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 less than 0.05) decrease of Bmax of (3H)-QNB (4.66 +/- 0.51 to 2.68 +/- 0.22 pmoles/mg protein). Addition of superoxide dismutase (SOD) and catalase (10 micrograms/ml) resulted in a significant reversal of Bmax value to 3.72 +/- 0.39 pmoles per mg protein (p less than 0.05). However, the affinity constants of dissociation (KD) 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 micrograms/ml catalase. The study demonstrates that the oxygen free radical species are capable of disrupting (3H)-QNB binding to the cardiac muscarinic receptors.
Arora
R C
RC
Hess
M L
ML
D000818:Animals; D004285:Dogs; D005609:Free Radicals; D006321:Heart / Q000294:innervation*; D006861:Hydrogen Peroxide / Q000633:toxicity; D006878:Hydroxides / Q000633:toxicity; D010100:Oxygen / Q000633:toxicity*; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism; D012508:Sarcolemma / Q000378:metabolism; D013481:Superoxides / Q000633:toxicity; D014969:Xanthine Oxidase
D005609:Free Radicals; D006878:Hydroxides; D011976:Receptors, Muscarinic; D013481:Superoxides; D011813:Quinuclidinyl Benzilate; D006861:Hydrogen Peroxide; D014969:Xanthine Oxidase; D010100:Oxygen