Tachykinin receptors and the airways.
The tachykinins, substance P, neurokinin A and neurokinin B, belong to a structural family of peptides. In mammalian airways, substance P and neurokinin A are colocalized to afferent C-fibres. Substance P-containing fibres are close to bronchial epithelium, smooth muscle, mucus glands and blood vessels. Sensory neuropeptides may be released locally, possibly as a result of a local reflex, and produce bronchial obstruction through activation of specific receptors on these various tissues. Three types of tachykinin receptors, namely NK-1, NK-2 and NK-3 receptors, have been characterized by preferential activation by substance P, neurokinin A and neurokinin B respectively. NK-1 and NK-2 receptors were recently cloned. The determination of receptor types involved in the effects of tachykinins in the airways has been done with synthetic agonists and antagonists binding specifically to NK-1, NK-2 and NK-3 receptors. Although the existence of species differences, the conclusion that bronchial smooth muscle contraction is mainly related to activation of NK-2 receptors on bronchial smooth muscle cell has been drawn. The hypothesis of a NK-2 receptor subclassification has been proposed with NK-2A receptor subtype in the guinea-pig airways. Other effects in the airways are related to stimulation of NK-1 receptors on mucus cells, vessels, epithelium and inflammatory cells. A non-receptor-mediated mechanism is also involved in the effect of substance P on inflammatory cells and mast cells.
Frossard
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N
Laboratoire de Physiologie Respiratoire, UFR Cochin Port Royal, Paris, France.
Advenier
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C
D000403:Airway Resistance; D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D008969:Molecular Sequence Data; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000502:physiology; D017981:Receptors, Neurotransmitter / Q000737:chemistry / Q000502:physiology; D018039:Receptors, Tachykinin; D012120:Respiration Disorders / Q000378:metabolism / Q000503:physiopathology; D012143:Respiratory Physiological Phenomena; D012137:Respiratory System / Q000098:blood supply / Q000737:chemistry*; D015320:Tachykinins / Q000502:physiology
D017981:Receptors, Neurotransmitter; D018039:Receptors, Tachykinin; D015320:Tachykinins