Cholinergic receptors

Cholinergic receptors are of two types – Muscarinic and Nicotinic receptors. Muscarinic receptors are named after Amanita muscaria are G protein coupled receptors and Nicotinic are ligand gated ion channel receptors.

Muscarinic receptors

Muscarinic receptors are named because of their activity related to muscarine, an alkaloid. These  are  G – protein receptors and binding of acetylcholine to muscarinic receptors can cause an inhibition of adenyl cyclase, activation of phospholipase C leading to formation of DAG or IP₃ and /or changes in ion channel activity.

Muscarinic receptors are blocked by atropine an alkaloid obtained from Atropa belladona. They are located primarily on the autonomic effector cells in the heart, blood vessels, eye, smooth muscles and glands of gastrointestinal, respiratory and urinary tracts, sweat glands etc. and in the central nervous system.

Subsidiary muscarinic receptors are also present in the autonomic ganglia where they appear to play a modulatory role by inducing a long lasting late EPSP.

Muscarinic autoreceptors are present prejunctionally on the post ganglionic cholinergic nerve endings. Activation of these receptors inhibits further release of acetylcholine.

There are five Muscarinic receptor subtypes M₁, M₂, M₃, M₄ and M₅. Of these receptors, M₁, M₂ and M₃ are important.

	M1	M2	M3
Location and function subserved	Autonomic ganglia– depolarization(Late EPSP) Gastric glands– histamine induced release of acid secretion CNS– no precise activity is documented till date	SA node – hyperpolarization Decreased rate of impulse generation AV node– decreased conduction velocity Atrium– decreased contractility Ventricles– decreased contractility	Visceral smooth muscle– contraction Exocrine glands– increases secretion
Nature	G -protein	G -protein	G -protein
Agonist	Oxotremorine	Methacholine	Bethanechol
Antagonist	Pirenzepine	Methoctramine	–

Nicotinic receptors

Nicotinic receptors are named for their selective activation by nicotine. They belong to the super family of ligand-gated ion channels. Binding of acetylcholine causes rapid opening of a nonselective cation channel, which depolarizes the postsynaptic or postjunctional cell.

Nicotinic receptors are activated by nicotine and blocked by d-tubocurarine or hexamethonium. There are two sub types of nicotinic receptors. They are N_M and N_N receptors.

1. N_M receptors are present in the skeletal muscle motor end plate. They mediate skeletal muscle contraction. These receptors are stimulated by phenyl trimethyl ammonium and blocked by d-tubocurarine.
2. N_N receptors are present in the parasympathetic and sympathetic ganglia, adrenal medulla, spinal cord and certain areas of brain. These receptors are also stimulated by phenyl trimethyl ammonium and blocked by hexamethonium.