6.2: Adrenergic Receptors (Adrenoceptors): Classification
Adrenergic receptors, or adrenoceptors, respond to the autonomic neurotransmitter noradrenaline and other endogenous catecholamine agonists. They are classified into two main families, α and β, based on their pharmacological response and are further subdivided depending on their location, elicited response, and affinity to specific agonists or antagonists.
α-Adrenoceptors
α-Adrenoceptors are classified into two main subtypes: α1 and α2. The α1 adrenoceptors, which are found on postsynaptic effector cells, mainly in smooth muscles, have three subtypes: α1A, α1B, and α1D. The α2 adrenoceptors are found in presynaptic adrenergic neurons, lipocytes, platelets, and smooth muscles and have three subtypes: α2A, α2B, and α2C.
ꞵ-Adrenoceptors
ꞵ-adrenoceptors have three subtypes: ꞵ1, ꞵ2, and ꞵ3. The β1 adrenoceptors are located postsynaptically on effector organs such as the heart, brain, and lipocytes. While presynaptically, they are located in adrenergic and cholinergic nerve terminals, renal juxtaglomerular cells, and ciliary epithelial cells. The β2 adrenoceptors are found on postsynaptic effector cells, cardiac and smooth muscles. They are also present postsynaptically in lipocytes and cardiac tissues.
Adrenoceptors Are Membrane-bound G protein–coupled Receptors
α1 adrenoceptor stimulation activates phospholipase C, producing IP3 and DAG as second messengers. α2 adrenoceptor activation inhibits adenylyl cyclase (decreasing cAMP level) and modulates Ca2+ and K+ ion channels. All types of β-adrenoceptors activate adenylyl cyclase.
α1 adrenoceptor stimulation constricts blood vessels, increases salivation, relaxes the GI smooth muscles, and increases hepatic glycogenolysis. α2 adrenoceptor stimulation, on the other hand, inhibits transmission and release of the autonomic neurotransmitters noradrenaline and acetylcholine, platelet aggregation, vascular smooth muscle contraction, and insulin release inhibition. Stimulation of β1 adrenoceptor increases heart rate and contraction force. β2 adrenoceptor stimulation causes bronchodilatation, vasodilatation, visceral smooth muscle relaxation, hepatic glycogenolysis, and muscle tremors. β3 adrenoceptor stimulation is responsible for lipolysis, thermogenesis, and relaxation of the detrusor muscle in the bladder.
