Influence of pH on the binding of scopolamine and N-methylscopolamine to muscarinic receptors in the corpus striatum and heart of rats.

The influence of pH on the binding of scopolamine and [3H]N-methylscopolamine to muscarinic receptors in the heart and corpus striatum was investigated. The specific binding of [3H]N-methylscopolamine in the heart and corpus striatum was relatively insensitive to pH over the range of 6 through 10 but decreased markedly below pH 6.0. This reduction in binding was attributed to a reversible decrease in the observed affinity without an effect on the binding capacity. The data are consistent with the postulate that [3H]N-methylscopolamine competes with hydrogen ions for an acidic group on the muscarinic receptor that has a pKA of approximately 5.5 in both the heart and corpus striatum. When measured by competitive inhibition of the binding of [3H]N-methylscopolamine, the affinity of scopolamine decreased relative to that of [3H]N-methylscopolamine as the pH increased from 6 to 10, confirming that it is primarily the protonated form of scopolamine that binds with muscarinic receptors.