Autonomic Receptors

Historically, structure-activity analyses, with careful comparisons of the potency of series of autonomic agonist and antagonist analogs, led to the definition of different autonomic receptor subtypes, including muscarinic and nicotinic cholinoceptors, and alpha, beta, and dopamine adrenoceptors. Subsequently, binding of isotope-labeled ligands permitted the purification and characterization of several of the receptor molecules. Molecular biology now provides techniques for the discovery and expression of genes that code for related receptors within these groups

Major Autonomic Receptor Types.

Receptor Name Typical Locations Result of Ligand Binding Cholinoceptors    Muscarinic M1   CNS neurons, sympathetic postganglionic neurons, some presynaptic sites Formation of IP3 and DAG, increased intracellular calcium     Muscarinic M2   Myocardium, smooth muscle, some presynaptic sites; CNS neurons Opening of potassium channels, inhibition of adenylyl cyclase   Muscarinic M3   Exocrine glands, vessels (smooth muscle and endothelium); CNS neurons Like M1 receptor-ligand binding     Muscarinic M4   CNS neurons; possibly vagal nerve endings Like M2 receptor-ligand binding     Muscarinic M5   Vascular endothelium, especially cerebral vessels; CNS neurons Like M1 receptor-ligand binding     Nicotinic NN   Postganglionic neurons, some presynaptic cholinergic terminals Opening of Na+,K+ channels, depolarization     Nicotinic NM   Skeletal muscle neuromuscular end plates Opening of Na+,K+ channels, depolarization   Adrenoceptors    Alpha1   Postsynaptic effector cells, especially smooth muscle Formation of IP3 and DAG, increased intracellular calcium     Alpha2   Presynaptic adrenergic nerve terminals, platelets, lipocytes, smooth muscle Inhibition of adenylyl cyclase, decreased cAMP   Beta1   Postsynaptic effector cells, especially heart, lipocytes, brain; presynaptic adrenergic and cholinergic nerve terminals, juxtaglomerular apparatus of renal tubules, ciliary body epithelium Stimulation of adenylyl cyclase, increased cAMP   Beta2   Postsynaptic effector cells, especially smooth muscle and cardiac muscle Stimulation of adenylyl cyclase and increased cAMP. Activates cardiac Gi under some conditions.     Beta3   Postsynaptic effector cells, especially lipocytes; heart Stimulation of adenylyl cyclase and increased cAMP1   Dopamine receptors    D1 (DA1), D5   Brain; effector tissues, especially smooth muscle of the renal vascular bed Stimulation of adenylyl cyclase and increased cAMP   D2 (DA2)   Brain; effector tissues, especially smooth muscle; presynaptic nerve terminals Inhibition of adenylyl cyclase; increased potassium conductance D3   D3 Brain Inhibition of adenylyl cyclase D4     D4   Brain, cardiovascular system Inhibition of adenylyl cyclase

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The primary acetylcholine receptor subtypes were named after the alkaloids originally used in their identification: muscarine and nicotine, thus muscarinic and nicotinic receptors. In the case of receptors associated with noradrenergic nerves, the use of the names of the agonists (noradrenaline, phenylephrine, isoproterenol, and others) was not practicable. Therefore, the term adrenoceptor is widely used to describe receptors that respond to catecholamines such as norepinephrine. By analogy, the term cholinoceptor denotes receptors (both muscarinic and nicotinic) that respond to acetylcholine. In North America, receptors were colloquially named after the nerves that usually innervate them; thus, adrenergic (or noradrenergic) receptors and cholinergic receptors. The general class of adrenoceptors can be further subdivided into alpha-adrenoceptor, beta-adrenoceptor, and dopamine-receptor types on the basis of both agonist and antagonist selectivity and on genomic grounds. Development of more selective blocking drugs has led to the naming of subclasses within these major types; for example, within the alpha-adrenoceptor class, alpha₁ and alpha₂ receptors differ in both agonist and antagonist selectivity.

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