title: Tachykinins, sensory nerves, and asthma--an overview.
abstract: Tachykinin peptides, substance P (SP) and neurokinin A (NKA), are released from airway sensory nerves upon exposure to irritant chemicals and endogenous agents including bradykinin, prostaglandins, histamine, and protons, The released neuropeptides are potent inducers of a cascade of responses, including vasodilatation, mucus secretion, plasma protein extravasation, leukocyte adhesion--activation, and bronchoconstriction. Neurokinin 1 receptors (preferably activated by SP) seem to be most important for inflammatory actions, while neurokinin 2 receptors (preferably activated by NKA) mediate bronchoconstriction. Species differences exist whereby rat and guinea-pig have a more developed neurogenic inflammation response than normal human airways. However, disease states such as inflammation or viral infections lead to enhanced peptide synthesis and (or) increased sensory nerve excitability. Together with increased neurokinin 1 receptor synthesis and loss of major tachykinin-degrading enzymes such as neutral endopeptidase in airway inflammation, this suggests that recently developed, orally active nonpeptide neurokinin receptor antagonists could have a therapeutic potential in asthmatic patients.
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
authors.forename: J M
authors.initials: JM
authors.lastname: Lundberg
mesh_terms: D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000209:etiology*; D001980:Bronchi / Q000294:innervation; D016084:Bronchoconstriction; D006801:Humans; D064729:Neurokinin-1 Receptor Antagonists; D009475:Neurons, Afferent / Q000502:physiology*; D018040:Receptors, Neurokinin-1 / Q000502:physiology; D013045:Species Specificity; D015320:Tachykinins / Q000502:physiology*
chemical_list: D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1; D015320:Tachykinins