Neurokinin3 receptor regulation of the airways.
Neurokinin(3) (NK(3)) receptors may regulate the airways primarily through actions on the nerves. In the periphery, airway parasympathetic ganglia neurons are depolarized following NK(3) receptor activation resulting subsequently in the facilitation of synaptic transmission. Such an effect may account for the excessive parasympathetic reflex effects (e.g. airway smooth muscle contraction, vascular engorgement, mucus secretion) associated with asthma and chronic obstructive pulmonary disease (COPD). In the central nervous system (CNS), NK(3) receptor activation may regulate airway vagal afferent relay neurons, rendering them hyperresponsive to parallel inputs from glutamate containing afferent nerves. This process is analogous to the process of central sensitization regulating hyperalgesia and pain in somatic tissues. In both the CNS and in the airways, NK(3) receptors are likely activated by either substance P and/or neurokinin A (NKA), both of which are full agonists at NK(3) receptors, as there is little evidence that airway nerves express neurokinin B (NKB). Evidence for other potential sites of regulation by NK(3) receptors in the airways (e.g. vasculature, airway smooth muscle, epithelium, mucus glands) is either inconclusive or conflicting.
Canning
Brendan J
BJ
Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, Maryland 21224, United States. bjc@jhmi.edu
D000818:Animals; D002490:Central Nervous System / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D008959:Models, Neurological; D015288:Neurokinin A / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology; D018042:Receptors, Neurokinin-3 / Q000819:agonists / Q000502:physiology*; D013373:Substance P / Q000494:pharmacology
D018377:Neurotransmitter Agents; D018042:Receptors, Neurokinin-3; D013373:Substance P; D015288:Neurokinin A