Histamine and airway caliber.
Since Dale and Laidlaw first produced airway obstruction in animals by infusing histamine, much has been done to understand the role of histamine in hyperreactive airway diseases. Histamine has been found to activate three subtypes of receptors: the H1 subtype, which mediates a number of cellular events resulting in airway obstruction; the H2 subtype, which plays an unclear and perhaps variable role in mediating airway caliber changes; and the newly described H3 subtype, which has not yet been studied in relation to airway caliber. The mechanisms involved in the synthesis, storage, and release of histamine from mast cells and basophils have been described. Pulmonary cells responsible for airway obstruction via H1 receptor stimulation have been identified and include bronchial smooth muscle, epithelial, endothelial, and pulmonary macrophage cells. Radioligand binding studies have begun to characterize the density and affinity of pulmonary H1 receptors. Intracellular events following H1 receptor stimulation have been shown to include calcium influx, phosphatidyl-inositol turnover, increases in cGMP, and the synthesis of prostaglandins. Despite a great deal of effort to define the relation between histamine and the parasympathetic nervous system, their exact interactions leading to changes in airway caliber remain to be resolved. Many pathologic conditions and mediators related to inflammation have been shown to increase histamine-induced airway responsiveness. A few endogenous mediators and a number of pharmacologic agents have been shown to decrease histamine-induced airway responsiveness. Although much has been done to elucidate the role of histamine and the H1 receptor system in modulating airway caliber, much more needs to be done to fully understand the complexities and significance of the H1 receptor system in normal and pathologic states of the airway.(ABSTRACT TRUNCATED AT 250 WORDS)
Joad
J
J
University of Illinois College of Medicine, Chicago.
Casale
T B
TB
D000818:Animals; D001249:Asthma / Q000503:physiopathology; D006632:Histamine / Q000502:physiology*; D006633:Histamine Antagonists; D006801:Humans; D010275:Parasympathetic Nervous System / Q000502:physiology; D011969:Receptors, Histamine H1 / Q000502:physiology; D011970:Receptors, Histamine H2 / Q000502:physiology; D012137:Respiratory System / Q000033:anatomy & histology*
D006633:Histamine Antagonists; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D006632:Histamine