title: Pathogenesis of asthma. Neurophysiology and pharmacology of bronchospasm.
abstract: Asthma results from variable and often sudden changes in airway smooth muscle tone. Allergy is not an essential component of the asthmatic response; however, mediator release plays an important role in the human asthmatic response. Histamine may act directly to cause bronchoconstriction by stimulating the H1-receptor on airway smooth muscle or indirectly by stimulation of afferent vagal fibers in airways. Histamine may also act locally on airways to augment cholinergic and, possibly, alpha-adrenergic constrictor effects, or to antagonize beta-adrenergic relaxation of airway smooth muscle. Cholinergic neural output promotes bronchoconstriction in non-atopic asthma, but parasympathetic reflexes are not a major component of human bronchial responses to inhaled allergen. The physiologic significance of the sympathetic nervous system in relaxing airway smooth muscle is incompletely defined. Recent studies suggest that direct sympathetic innervation of airways is relatively unimportant and that purinergic fibers may be the predominant inhibitory neurons in human airways. Investigations focusing on intracellular calcium metabolism in airway smooth muscle have implicated the adenyl cyclase-cyclic adenosine monophosphate system in the regulation of bronchomotor tone. Cyclic nucleotides may modulate but do not mediate respiratory muscle contraction, and their precise role in regulating bronchomotor tone remains uncertain.
mesh_terms: D000328:Adult; D000818:Animals; D001249:Asthma / Q000209:etiology / Q000503:physiopathology*; D001341:Autonomic Nervous System / Q000187:drug effects; D001980:Bronchi / Q000187:drug effects / Q000294:innervation; D001986:Bronchial Spasm / Q000503:physiopathology; D002648:Child; D000242:Cyclic AMP / Q000378:metabolism; D004285:Dogs; D006801:Humans; D009638:Norepinephrine / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000378:metabolism; D011969:Receptors, Histamine H1 / Q000378:metabolism; D012130:Respiratory Hypersensitivity / Q000150:complications
chemical_list: D011941:Receptors, Adrenergic; D011950:Receptors, Cholinergic; D011969:Receptors, Histamine H1; D000242:Cyclic AMP; D009638:Norepinephrine