Paraoxon-induced decrease in the muscarinic acetylcholine receptor content in rat heart.

The regulation of the rat heart muscarinic acetylcholine receptor by injection of paraoxon (an acetylcholinesterase inhibitor) was characterized. No changes in receptor density in the four cardiac chambers were seen after two days. After three daily injections, however, significant decreases (20-25%) were observed in both atria and ventricles. These changes were associated with a 50% decrease in cardiac acetylcholinesterase activity. We were unable to demonstrate a change in the proportion or value of the apparent KDs for the two previously described affinity states of the receptor for the agonist methacholine. We found that the proportion of the high affinity form of the receptor was greater in atria than in ventricle (70 vs. 55%). Moreover, we also found that acetylcholinesterase activity was greater in the atria than ventricle. Although methacholine will produce down regulation of the muscarinic receptor in the perfused rat heart in 2.5 h (Reinhardt and Roskoski, 1983; J. Pharmacol. Exp. Ther. 226, 135), injection of large doses of methacholine failed to produce any receptor decreases within 6 h in vivo.