Adrenoceptors

Adrenoceptors, also known as adrenergic receptors, are a family of G protein–coupled receptors that transduce signals from the catecholamines norepinephrine and epinephrine. They are widely expressed in the central nervous system and peripheral tissues, where they mediate key sympathetic nervous system responses.

The receptors are traditionally classified into two main types, alpha (α) and beta (β), with several subtypes. The α1 group includes α1A, α1B, and α1D; the α2 group includes α2A, α2B, and α2C. The β group includes β1, β2, and β3. α1 and β receptors are coupled to stimulatory G proteins, whereas α2 receptors are coupled to inhibitory G proteins. Specifically, α1 receptors activate phospholipase C via Gq, α2 receptors inhibit adenylyl cyclase via Gi, and β1/β2/β3 receptors activate adenylyl cyclase via Gs.

Physiologically, α1 receptors promote vasoconstriction in vascular smooth muscle and pupillary dilation. α2 receptors modulate neurotransmitter release through negative feedback. β1 receptors are prominent in the heart, increasing heart rate and contractility and influencing renin release; β2 receptors promote bronchodilation and vasodilation in skeletal muscle, and β3 receptors stimulate lipolysis in adipose tissue. Metabolic and vascular effects vary by tissue distribution of each subtype.

Endogenous ligands epinephrine and norepinephrine activate these receptors, coordinating the fight-or-flight response. Pharmacologically, selective and nonselective agonists and antagonists are used to treat cardiovascular, respiratory, and metabolic conditions. Examples include phenylephrine (α1 agonist), prazosin (α1 antagonist), clonidine (α2 agonist), propranolol (nonselective β blocker), metoprolol (β1 blocker), albuterol (β2 agonist), and mirabegron (β3 agonist). Receptor regulation and desensitization also influence therapeutic outcomes in conditions such as hypertension and heart failure.