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Muscarinic Receptor

  • Muscarinic Receptors bind acetylcholine and are located in a variety of visceral organs innervated by the parasympathetic nervous system. These receptors take their name from the fact that they are specifically activated by Muscarin and represent a distinct class from nicotinic acetylcholine receptors. Although all muscarinic receptors are G-protein coupled receptors, excitatory and inhibitory subtypes exist.
Subtypes and Mechanism of Action
  • Five muscarinic receptor subtypes have been described termed M1-M5. In general, the odd numbered receptors (M1, M3, M5) lead to cellular excitation by activation of Gq whereas the even numbered receptors lead to cellular inhibition by activation of Gi. A review of G-protein coupled receptors elsewhere may be helpful at this point to review the downstream signaling of Gq and Gi subunits of G-proteins.
Physiological Anatomy
  • Overview
    • Muscarinic Receptors are found on all target organs innervated by parasympathetic nervous system and are responsible for the diverse physiological effects of parasympathetic output. They are also the target receptor for sympathetic fibers that specifically innervate sweat glands. Organ-specific expression of specific muscarinic subtypes has been described but familiarity with these expression patterns is not necessary at this level. Below we largely copy our discussion of the physiological anatomy of the parasympathetic nervous system as its physiological output is largely mediated by that of muscarinic receptors.
  • Eyes
    • Promotes pupillary constriction (i.e. miosis) by stimulating contraction of the circular muscle of the iris. Muscarinic receptors on the ciliary muscle trigger it to constrict which leads to relaxation of the lens, thus allowing for focusing on near objects.
  • Glandular Secretion
  • GI Motility
    • Although GI motility is directly controlled by the enteric nervous system, muscarinic receptors stimulated by parasympathetic fibers can modulate its activity. In general, stimulation promotes peristalisis and relaxation of GI sphincters. These effects are discussed in more detail under Autonomic GI Neural Control.
  • Heart
    • Parasympathetic stimulation of cardiac muscarinic receptors generally leads to reduced contractility, sinus rate, and AV nodal conduction. Together these negative inotropic, chronotropic, and dromotropic effects reduce the heart rate and cardiac output as discussed in detail under Autonomic Cardiac Regulation.
  • Vasculature
    • Muscarinic Receptors are found on the vessel wall and their stimulation does lead to vasodilation via a Nitric Oxide-mediated. However, these muscarinic receptors appear to play little to no physiological role in controlling peripheral resistance as vessels are not innervated by the parasympathetic nervous system. However, they can be stimulated by parenteral administration of acetylcholine and explain its vasodilatory effect.
  • Lungs
    • Parasympathetic stimulation of in bronchiolar muscarinic receptors results in bronchoconstriction and thus increased airflow resistance.
  • Genitourinary System
    • Bladder: Parasympathetic output to muscarinic receptors results in contraction of the detrusor muscle and relaxation of the internal urethral sphincter, thus promoting micturition.
    • Penis: Stimulation of muscarinic receptors by the parasympathetic nervous system is critical for triggering and maintaining an erection.