TY - JOUR T1 - ACTIONS OF SYMPATHOMIMETIC AMINES AND THEIR ANTAGONISTS ON SKELETAL MUSCLE JF - Pharmacological Reviews JO - Pharmacol Rev SP - 27 LP - 72 VL - 21 IS - 1 AU - W. C. BOWMAN AU - M. W. NOTT Y1 - 1969/03/01 UR - http://pharmrev.aspetjournals.org/content/21/1/27.abstract N2 - Epinephrine exerts a direct action on mammalian muscle fibers which is mediated via β-receptors. Activation of these receptors results in prolongation of the active state of white, fast-contracting muscles and curtailment of the active state of red, slow-contracting muscles. In chronically denervated mammalian muscles of both types, and in chronically denervated avian muscles, activation of the β-receptors increases the fibrillary discharge and the tone exerted by the muscles. It is suggested that these effects on muscle contractility may arise through activation of the adenyl cyclase/cyclic 3' ,5'-AMP system, which in turn leads to changes in the rates of uptake of Ca2+ by the sarcoplasmic reticulum. Activation of the β-receptors also increases the muscle demarcation potential, presumably as a result of hyperpolarization of the muscle fiber membranes. Under sensitive conditions, this effect can be shown to lead to a depressant effect on neuromuscular transmission. Epinephrine also exerts an initial faciitatory action on neuromuscular transmission in all types of muscle, and this is mediated via α-receptors, probably located in the motor nerve endings, activation of which appears to cause an inincrease in the amount of acetylcholine released by the nerve impulse. Hyperpolarization of motor nerve endings increases release of transmitter by nerve impulses, and epinephrine may act by hyperpolarizing some part of the terminal membrane. It may be that, although mediated by different types of receptor, epinephrine exerts an effect on the coupling of excitation and transmitter release in nerve which is analogous to its action on excitation-contraction coupling in muscle, both effects involving changes in the levels of free calcium ions. Cyclic 3' ,5'-AMP may also be a mediator in the facilitatory effect on neuromuscular transmission, and this fact implies the unusual situation that, in nerve, increased levels of the nucleotide may be evoked through α-receptors. The defatiguing action of epinephrine and sympathetic stimulation in mammalian fast-contracting muscles mainly involves the prejunctional α-receptors, but the postjunctional β-receptors also contribute. In fatigued frog muscle, only prejunctional α-receptors are involved. Apart from an indirect action arising from circulatory changes, epinephrine is without a defatiguing effect in red, slow-contracting mammalian muscles. A consideration of the effective doses of catecholamines suggests that only the action of epinephrine on the sensitive slow-contracting red muscle fibers has any physiological significance. This action is probably responsible for the enhancement of physiological tremor and of Parkinsonian tremor produced by catecholamines in man, and for the tremor often associated with phaeochromocytoma. 1969 by The Williams & Wilkins Co. ER -