α1-Receptors are postsynaptic adrenoceptors located in smooth muscle throughout the body (in the eye, lung, blood vessels, uterus, gut, and genitourinary system). Activation of these receptors increases intracellular calcium ion concentration, which leads to the contraction of smooth muscles. Thus, α1-agonists are associated with mydriasis (pupillary dilation due to contraction of the radial eye muscles), bronchoconstriction, vasoconstriction, uterine contraction, and constriction of sphincters in the gastrointestinal and genitourinary tracts. Stimulation of α1-receptors also inhibits insulin secretion and lipolysis. The myocardium possesses α1-receptors that have a positive inotropic effect, which might play a role in catecholamine-induced arrhythmia. Nonetheless, the most important cardiovascular effect of α1 stimulation is vasoconstriction, which increases peripheral vascular resistance, left ventricular afterload, and arterial blood pressure.
In contrast to α1-receptors, α2-receptors are located primarily on the presynaptic nerve terminals. Activation of these adrenoceptors inhibits adenylyl cyclase activity. This decreases the entry of calcium ions into the neuronal terminal, which limits subsequent exocytosis of storage vesicles containing norepinephrine. Thus, α2-receptors create a negative feedback loop that inhibits further norepinephrine release from the neuron. In addition, vascular smooth muscle contains postsynaptic α2-receptors that produce vasoconstriction. More importantly, stimulation of postsynaptic α2-receptors in the central nervous system causes sedation and reduces sympathetic outflow, which leads to peripheral vasodilation and lower blood pressure.
β-Adrenergic receptors are classified into β1-, β2-, and β3-receptors. Norepinephrine and epinephrine are equipotent on β1-receptors, but epinephrine is significantly more potent than norepinephrine on β2-receptors. The much more potent actions of norepinephrine on α-receptors tends to obscure any differences between epinephrine and norepinephrine on β-receptors when these drugs are infused in patients.
β1-Receptors are located on the postsynaptic membranes in the heart. Stimulation of these receptors activates adenylyl cyclase, which converts adenosine triphosphate to cyclic adenosine monophosphate and initiates a kinase phosphorylation cascade. Initiation of the cascade has positive chronotropic (increased heart rate), dromotropic (increased conduction), and inotropic (increased contractility) effects.
β2-Receptors are postsynaptic adrenoceptors primarily located in smooth muscle and gland cells, but they are also located in ventricular myocytes. They share a common mechanism of action with β1-receptors: adenylyl cyclase activation. Despite this commonality, β2 stimulation relaxes smooth muscle, resulting in bronchodilation, vasodilation, and relaxation of the uterus (tocolysis), bladder, and gut. Glycogenolysis, lipolysis, gluconeogenesis, and insulin release are stimulated by β2-receptor activation.
β3-Receptors are found in the gallbladder and brain adipose tissue. Their role in gallbladder physiology is unknown, ...