M1/M3 - Muscarinic Receptors (Ach)

Activation of M1/M3 muscarinic responses.
Stimulation of M1-muscarinic receptors by acetylcholine leads to the activation of a Gq coupling protein. The alpha subunit of this G protein activates the effector, phospholipase C, which leads to the release of IP3 (inositol 1,4,5-trisphosphate) and DAG (diacylglycerol) from phosphatidylinositol 4,5-bisphosphate (PtdIns 4,5-P2). IP3 stimulates the release of sequestered stores of calcium, leading to an increased concentration of cytoplasmic Ca2+. Ca2+ may then activate Ca2+-dependent protein kinases, which in turn phosphorylate their substrates. DAG activates protein kinase C.
M3-Muscarinic receptors cause contraction of smooth muscle in the following organs:

• Eye: sphincter of the iris
• Eye: ciliary muscle
• Lungs: tracheal and bronchial muscle
• Stomach and Intestines: increase motility and parasympathetic tone
• Glands (lacrimal, salivary, bronchial, pancreatic, mucosal, and sweat(sympathetic), adrenal(sympathetic)): increase secretion
• Bladder: detrusor muscle
• Sex Organs, Male: M3-receptors cause release of nitric oxide in endothelial cells producing vasodilation (erection)

Adapted from Figure 9-1: StatRef Online Library: Basic and Clinical Pharmacology 8th ed. (2001)
by Michael Bolger, 8/26/01
Copyright(c) 2001 The McGraw Hill Companies, Inc. All rights reserved