Pre- and Postsynaptic Effects of Muscarinic Antagonists in the Isolated Guinea Pig Ileum

Abstract

Several compounds have been claimed to differentiate between subtypes of muscarinic receptors (2). In the experiments described in this chapter we have studied in the guinea-pig ileum whether the presynaptic muscarinic receptors of the cholinergic nerves differ from the postsynaptic muscarinic receptors of the longitudinal muscle in their affinities for several muscarinic antagonists (methylatropine; trihexyphenidyl; clozapine; DAMP). Inhibition by oxotremorine of the evoked release of acetylcholine (ACh) was used as a parameter of presynaptic activity, and the increase by oxotremorine of smooth muscle tension as a postsynaptic parameter. The affinity constants (pA₂ values) of the antagonists were determined by constructing complete concentration response curves for pre- and postsynaptic effects of oxotremorine, in the absence and presence of different concentrations of the respective antagonist. Differences in the affinities of a given antagonist to either pre- or postsynaptic receptors should result in different pre- and postsynaptic pA₂ values.