Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1323099 (sympathomimetic)
 2,957 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic and acute administration of epinephrine or related sympathomimetic agents are typically prescribed for the treatment of clinical disorders such as hypotension, anaphylactic and allergic reactions, and bronchial asthma. In addition to its effects on these infirmaties and on carbohydrate metabolism, epinephrine also exerts a positive inotropic effect on fast-contracting skeletal muscle in a variety of animal species. At present, the precise mechanisms responsible for the inotropic effect are not known. This communication reviews the positive inotropic effects of epinephrine on fast-contracting skeletal muscle and discusses possible mechanisms which might mediate this phenomenon. Epinephrine potentiates muscle twitches via the second messenger, cAMP, secondary to hormone binding to membrane-bound beta-receptors. Cyclic AMP then acts to increase carbohydrate metabolism, alter sodium/potassium exchange, phosphorylate myosin isozymes, and/or alter intracellular calcium exchange. Based on theoretical grounds, the first three mechanisms can be excluded. Therefore, it is tentatively hypothesized that the effect is due to cAMP-enhanced calcium exchange within the muscle fiber and/or to increased influx of extracellular calcium. This notion is consistent with the mechanism of the positive inotropic effects of epinephrine on cardiac tissue. If this hypothesis is correct, it would also suggest a role, at least under some conditions, for extracellular calcium in the process of skeletal muscle excitation-contraction coupling.
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PMID:The positive inotropic effect of epinephrine on skeletal muscle: a brief review. 269 40

The thermodynamic parameters associated with the interactions of agonists and antagonists with digitonin-solubilized beta adrenergic receptors were determined. A rapid method for measuring the binding of [125I]iodopindolol to soluble receptors using glass-fiber filters was developed. The binding of [125I]iodopindolol, an antagonist with intrinsic sympathomimetic activity, to soluble receptors was temperature-sensitive as is the binding of the ligand to membrane-bound receptors. The interactions of propranolol and timolol with soluble receptors were independent of temperature. In contrast, the binding of agonists to soluble receptors was sensitive to temperature, although insensitive to GTP. Thermodynamically, the interactions of the antagonists timolol and propranolol with soluble beta adrenergic receptors were entropy-driven, with little contribution from changes in enthalpy. This is consistent with a hydrophobic interaction between the receptor and the antagonist. The binding of [125I]iodopindolol was enthalpy-driven. The binding of full agonists with soluble receptors was described thermodynamically by changes in enthalpy and entropy that were negative relative to the values for propranolol and timolol, suggesting that the guanine nucleotide-binding protein required for stimulation of adenylate cyclase activity and an intact lipid environment are not involved in the thermodynamics of formation of the low-affinity component of agonist binding. These results are consistent with an agonist-induced change in the conformation of the receptor.
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PMID:Thermodynamic properties of agonist interactions with the beta adrenergic receptor-coupled adenylate cyclase system. II. Agonist binding to soluble beta adrenergic receptors. 287 Jan 75