Muscarinic Agonists and Antagonists: Effects on Gastrointestinal Function
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Muscarinic agonists and antagonists are used to treat a handful of gastrointestinal (GI) conditions associated with impaired salivary secretion or altered motility of GI smooth muscle. With regard to exocrine secretion, the major muscarinic receptor expressed in salivary, gastric, and pancreatic glands is the M3 with a small contribution of the M1 receptor. In GI smooth muscle, the major muscarinic receptors expressed are the M2 and M3 with the M2 outnumbering the M3 by a ratio of at least four to one. The antagonism of both smooth muscle contraction and exocrine secretion is usually consistent with an M3 receptor mechanism despite the major presence of the M2 receptor in smooth muscle. These results are consistent with the conditional role of the M2 receptor in smooth muscle. That is, the contractile role of the M2 receptor depends on that of the M3 so that antagonism of the M3 receptor eliminates the response of the M2. The physiological roles of muscarinic receptors in the GI tract are consistent with their known signaling mechanisms. Some so-called tissue-selective M3 antagonists may owe their selectivity to a highly potent interaction with a nonmuscarinic receptor target.
Gastrointestinal Agents pharmacology, Gastrointestinal Tract drug effects, Muscarinic Agonists pharmacology, Muscarinic Antagonists pharmacology, Parasympathetic Nervous System drug effects, Receptors, Muscarinic drug effects
Digestive System | Other Pharmacy and Pharmaceutical Sciences
Ehlert, Frederick J., Kirk J. Pak, and Michael T. Griffin. "Muscarinic agonists and antagonists: effects on gastrointestinal function." In A.D. Fryer, A. Christopoulous, and N.M. Nathonson (Eds.), Muscarinic Receptors. Berlin: Springer Berlin Heidelberg, 2012. 343-374.