Mitigation of chlorine lung injury by increasing cyclic AMP levels.
Chlorine is considered a chemical threat agent to which humans may be exposed as a result of accidental or intentional release. Chlorine is highly reactive, and inhalation of the gas causes cellular damage to the respiratory tract, inflammation, pulmonary edema, and airway hyperreactivity. Drugs that increase intracellular levels of the signaling molecule cyclic AMP (cAMP) may be useful for treatment of acute lung injury through effects on alveolar fluid clearance, inflammation, and airway reactivity. This article describes mechanisms by which cAMP regulates cellular processes affecting lung injury and discusses the basis for investigating drugs that increase cAMP levels as potential treatments for chlorine-induced lung injury. The effects of beta(2)-adrenergic agonists, which stimulate cAMP synthesis, and phosphodiesterase inhibitors, which inhibit cAMP degradation, on acute lung injury are reviewed, and the relative advantages of these approaches are compared.
Hoyle
Gary W
GW
Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, 319 Abraham Flexner Way, Louisville, KY 40202, USA. Gary.Hoyle@louisville.edu
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002713:Chlorine / Q000633:toxicity*; D000242:Cyclic AMP / Q000502:physiology*; D005740:Gases / Q000633:toxicity*; D006801:Humans; D019570:Inhalation Exposure; D008168:Lung / Q000187:drug effects*; D008171:Lung Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D051379:Mice; D023421:Models, Animal; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*
D000318:Adrenergic beta-Agonists; D005740:Gases; D010726:Phosphodiesterase Inhibitors; D002713:Chlorine; D000242:Cyclic AMP