5.5: Cholinergic Receptors: Muscarinic
The pharmacological actions of acetylcholine are elicited via its binding to two families of cholinergic receptors or cholinoceptors, namely, muscarinic and nicotinic receptors. Muscarinic receptors are G protein-coupled receptors and have five subtypes, M1–M5. All mAChR subtypes are activated by acetylcholine and blocked by the antagonist, atropine.
The subtypes M1, M3, and M5 couple with the Gq subunit and activate the phospholipase C (PLC) activity, mobilizing intracellular Ca2+. Activation of PLC proceeds with the production of secondary messengers, inositol-1,4,5-phosphate (IP3) and diacylglycerol (DAG). IP3 ion-channel receptor stimulation releases intracellular Ca2+ from the endoplasmic reticulum. DAG and Ca2+ activate protein kinase C (PKC), which phosphorylates protein to generate physiological effects.
The subtypes M2 and M4 couple with the Gi subunit to decrease adenylyl cyclase activity and increase K+ conductance. This reduces cyclic adenosine monophosphate (cAMP), activates inwardly rectifying potassium currents, and inhibits voltage-gated Ca2+ channels. The result is inhibition and hyperpolarization of excitable membranes.
M1 receptors, also called neural receptors, are primarily located in the CNS, PNS, and parietal cells. These receptors regulate gastrointestinal secretions following vagal stimulation, learning, motor function, and memory. M2 receptors, also called cardiac receptors, are majorly located in the heart and regulate negative inotropic and chronotropic effects while simultaneously stimulating smooth muscle contractions. M3 receptors are abundantly present in the smooth muscles and glands, where their activation stimulates muscle contraction and gland secretion. M4 and M5 receptors are located within the CNS and limit transmitter release.
