Adrenoceptor Subtypes and Catecholamine Actions

Smooth muscle effects. The opposing effects on smooth muscle (A) of a-and p-adrenoceptor activation are due to differences in signal transduction (p. 66). This is exemplified by vascular smooth muscle (A). ai-Receptor stimulation leads to intracellular release of Ca + via activation of the inositol tris-phosphate (IP3) pathway. In concert with the protein calmodulin, Ca + can activate myosin kinase, leading to a rise in tonus via phosphorylation of the contractile protein myosin. cAMP inhibits activation of myosin kinase. Via the former effector pathway, stimulation of a-receptors results in vasoconstriction via the latter, P2-receptors mediate vasodilation, particularly in skeletal muscle - an effect that has little therapeutic use. 

Vasoconstriction. Local application of a-sympathomimetics can be employed in infiltration anesthesia (p. 204) or for nasal decongestion (naphazoline, tetra-hydrozoline, xylometazoline pp. 90, 324). Systemically administered epinephrine is important in the treatment of anaphylactic shock for combating hypotension. 

Bronchodilation. P2-Adrenocep-tor-mediated bronchodilation (e.g., with terbutaline, fenoterol, or salbutamol) plays an essential part in the treatment of bronchial asthma (p. 328). 

Tocolysis. The uterine relaxant effect of P2-adrenoceptor agonists, such as terbutaline or fenoterol, can be used to prevent premature labor. Vasodilation Ltillmann, Color Atlas of Pharmacology ( 

Cardiostimulation. By stimulating Pi-receptors, hence activation of ade-nylatcyclase (Ad-cyclase) and cAMP production, catecholamines augment all heart functions, including systolic force (positive inotropism), velocity of shortening (p. clinotropism), sinoatrial rate (p. chronotropism), conduction velocity (p. dromotropism), and excitability (p. bathmotropism). In pacemaker fibers, diastolic depolarization is hastened, so that the firing threshold for the action potential is reached sooner (positive chronotropic effect, B). The cardiostim-ulant effect of p-sympathomimetics such as epinephrine is exploited in the treatment of cardiac arrest Use of p-sympathomimetics in heart failure carries the risk of cardiac arrhythmias. 

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