Muscarinic Receptor Subtypes in the GI Tract

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The differentiation between the muscarinic and the nicotinic ef- fects of acetylcholine led to the subdivision of the cholinergic ner- vous system into two categories. Further studies showed that stimu- lating and inhibiting muscarinic effects could be demonstrated in different organs. For instance, gastric secretion and gastrointestinal motility are stimulated, while heart rate and the vascular muscula- ture are inhibited. For decades, it could not be determined whether the various ef- fects were mediated by different subgroups of muscarinic receptors, but eventually, with the availability of agonists and antagonists to muscarinic receptors, and using various techniques, the existence of at least two such subgroups could be ascertained . . Mt receptors are defined by their high affinity for the antagonist pirenzipine in comparison to M2 receptors. This subdivision of muscarinic receptors has since been proved beyond doubt by experi- ments in vivo and in vitro, by receptor binding studies, by histoauto- radiography, and by electrophysiological studies. However, these different classes of muscarinic receptors have not been found to relate to different types of effects; instead both excit- atory and inhibitory effects appear to be linked to each class. For ex- ample, excitation of gut motility and inhibition of cardiac contrac- tile activities both appear to be mediated by M2 receptors, while ex- citation of some nerves in sympathetic ganglia and inhibition of some myenteric nerves may be mediated by M receptors.