adrenoceptor

Adrenoceptors, or adrenergic receptors, are a family of G protein-coupled receptors that respond to the catecholamines norepinephrine and epinephrine. In humans they are subdivided into alpha and beta categories, with several subtypes: alpha1 (A, B, D), alpha2 (A, B, C), beta1, beta2, and beta3.

Alpha1 receptors are primarily on vascular smooth muscle and cause vasoconstriction, leading to increased peripheral resistance; they also mediate pupil dilation and can promote contraction of the urinary sphincter. Alpha2 receptors are found on presynaptic nerve terminals and some postsynaptic sites; activation inhibits norepinephrine release and can decrease sympathetic outflow. Beta receptors stimulate various cardiovascular and metabolic responses: beta1 receptors in the heart increase heart rate and contractility; beta2 receptors in bronchial and some vascular smooth muscle cause bronchodilation and vasodilation; beta3 receptors in adipose tissue promote lipolysis.

Signal transduction for these receptors varies: alpha1 typically couples to Gq, activating phospholipase C and generating IP3 and DAG; alpha2 couples to Gi, inhibiting adenylyl cyclase; beta1/2/3 couple to Gs, stimulating adenylyl cyclase and increasing cAMP. Endogenous ligands are epinephrine and norepinephrine; selective and nonselective agonists and antagonists are used pharmacologically. Common agonists include phenylephrine (alpha1), clonidine (alpha2), albuterol (beta2), and isoproterenol (beta1/2). Antagonists include alpha1 blockers like prazosin, nonselective alpha blockers like phentolamine, and beta blockers such as propranolol (nonselective) and metoprolol (beta1 selective). Adrenoceptors play a central role in the regulation of cardiovascular, respiratory, metabolic, and autonomic functions, and are targets in treating hypertension, heart failure, asthma, COPD, glaucoma, and arrhythmias.