Cholinergic receptors

Acetylcholine is the transmitter at three different sites, autonomic ganglia, parasympathetic postganglionic nerve terminals and skeletal muscle motor nerve terminals. The action of acetylcholine on visceral effectors (smooth muscle of GIT, cardiac muscle and exocrine gland) resembles the action of the naturally occurring plant alkaloid muscarine. Therefore these receptors of acetylcholine on visceral effectors are called muscarinic receptors . Atropine blocks this receptor of acetylcholine. Acetylcholine in large dose exhibits its effects through ganglionic stimulation. This response resembles the effect of naturally occurring alkaloid nicotine. Thus, the response of acetylcholine on parasympathetic ganglia, sympathetic ganglia and adrenal medulla and neuromuscular junction are called nicotinic receptors . At the skeletal muscle motor plate the cholinergic receptors are nicotinic in nature; d-tubocurarine blocks these receptors in the skeletal muscle. The ganglionic nicotinic receptors are blocked by hexamethonium.

Fig. 2.8 Characteristic of important subtypes of muscarinic receptor

M ₁ , M ₂ and M ₃ are subtypes of muscarinic receptor. M1 receptor is G-protein coupled receptor which is linked with IP ₃ /DAG. This activated system will result in increase concentration of cytosolic calcium. And as we know calcium is responsible for long phase depolarization in autonomic ganglia and also result in release of histamine and acid from gland located GIT (gastrointestinal tract). Its action in CNS is unknown. M2 receptor is located in heart which is also G- protein coupled but its activation will down regulate the activity of c-AMP(cyclic adenosine monophosphate) and also responsible for the opening of potassium channel as both are responsible for decreased activity because of hyper polarization activity. As these receptors are found in heart they will decrease the generation of impulse as a result of this decrease heart rate and slow conduction of impulses. M3 is also IP ₃ /DAG linked but they are located on smooth muscle and exocrine glands will result in the contraction of muscles and secretion from gland because it will increase the cytosolic calcium.

Fig 2.9 Signal transduction

Characteristic of important subtypes of nicotinic receptor

Nicotinic receptors are of twtypes’ Nm and Nn. Nm is located in neuromuscular junction causes contraction of skeletal muscles because it causes depolarization of muscle end plate. Nn causes depolarization in autonomic ganglia result in post ganglionic impulse. Also cause release of catecholamine from adrenal medulla and also site specific excitation or inhibition in brain. Both Nm and Nn are Na ⁺ and k ⁺ channel linked but Nn also linked with an extra Ca ⁺⁺ channel.