Alpha-Adrenergic Receptors

• Adrenergic receptors, or adrenoceptors, are G protein-coupled receptors targeted by catecholamines, especially norepinephrine (noradrenaline) and epinephrine (adrenaline).
• Many cells possess adrenergic receptors; catecholamine binding generally triggers a sympathetic (or sympathomimetic) response.
• The two main classes of adrenergic receptors are α and β, with several subtypes.
• α-receptors have subtypes α1 and α2.
• β-receptors have subtypes β1, β2, and β3.
• Adrenergic receptors are activated by medications like beta blockers, β2 agonists, and α2 agonists, treating conditions like high blood pressure and asthma.

Alpha-Adrenergic Receptors (α-Adrenoceptors)

• α-receptors have two subtypes: α1 and α2.
• α1-receptors are located on postsynaptic sympathetic effector cells, such as smooth muscle.
• α2-receptors are located on presynaptic nerve terminals and, to a lesser extent, on postsynaptic effector cells.

α1-Adrenergic Receptors

• α1-adrenergic receptors are Gq-coupled receptors.
• They activate phospholipase C, increasing inositol trisphosphate (IP3) and diacylglycerol (DAG) levels.
• This results in increased intracellular calcium and activation of protein kinase C, leading to cellular effects.
• Stimulation of α1-receptors typically leads to smooth muscle contraction.
• Location: Smooth muscle cells in blood vessels, iris, and genitourinary system.
• Effects include vasoconstriction, increased blood pressure, mydriasis (pupil dilation), and contraction of the bladder sphincter.
• α1-agonists like phenylephrine are used as decongestants and to raise blood pressure.
• α1-antagonists like prazosin are used to treat hypertension and benign prostatic hyperplasia (BPH).

α2-Adrenergic Receptors

• α2-adrenergic receptors are Gi-coupled receptors.
• Activation of α2-receptors inhibits adenylyl cyclase, decreasing intracellular cAMP levels.
• This results in inhibition of neurotransmitter release, smooth muscle relaxation, and other cellular effects.
• Location: Presynaptic nerve terminals, platelets, and some smooth muscle cells.
• Effects include inhibition of norepinephrine release (negative feedback), platelet aggregation, and smooth muscle contraction.
• α2-agonists like clonidine are used to treat hypertension by reducing sympathetic outflow from the central nervous system.
• α2-antagonists like yohimbine have been used to treat erectile dysfunction and as a research tool.

Beta-Adrenergic Receptors (β-Adrenoceptors)

• β-receptors have three subtypes: β1, β2, and β3.
• All β-receptors are Gs-coupled receptors.
• They activate adenylyl cyclase, increasing cAMP levels.
• This results in activation of protein kinase A and subsequent phosphorylation of intracellular proteins, leading to various cellular effects.

β1-Adrenergic Receptors

• Location: Primarily in the heart and kidneys.
• Effects include increased heart rate (chronotropy), increased contractility (inotropy), and increased renin release from the kidneys.
• β1-agonists like dobutamine are used to treat heart failure.
• β1-antagonists (beta-blockers) like metoprolol are used to treat hypertension, angina, and arrhythmias.

β2-Adrenergic Receptors

• Location: Smooth muscle of the bronchioles, uterus, blood vessels, and liver.
• Effects include bronchodilation, vasodilation, relaxation of the uterus, and increased glycogenolysis and gluconeogenesis in the liver.
• β2-agonists like albuterol are used to treat asthma and other respiratory conditions by causing bronchodilation.
• Selective β2-agonists have fewer cardiac side effects than non-selective beta-agonists.

β3-Adrenergic Receptors

• Location: Primarily in adipose tissue.
• Effects include lipolysis (breakdown of fat) and thermogenesis.
• β3-agonists like mirabegron are used to treat overactive bladder by relaxing the detrusor muscle.

Receptor Selectivity

• Norepinephrine (noradrenaline) has a higher affinity for α-receptors than β-receptors, particularly α1-receptors.
• Epinephrine (adrenaline) has a relatively equal affinity for α- and β-receptors.
• Isoproterenol is a synthetic catecholamine with high affinity for β-receptors.
• The selectivity of drugs for different adrenergic receptor subtypes allows for targeted therapeutic effects with fewer side effects.

Adrenergic receptors are G protein-coupled receptors targeted by catecholamines, especially norepinephrine and epinephrine. The two main classes of adrenergic receptors are α and β, with subtypes. α-receptors have subtypes α1 and α2 and are located on postsynaptic sympathetic and presynaptic nerve terminals.