Antigen inhalation unmasks NK-2 tachykinin receptor-mediated responses in vagal afferents.
The majority of airway sensory innervation originates from afferent neurons whose somata reside in vagal (nodose and jugular) ganglia. Using guinea pigs immunized with chick ovalbumin, we have discovered that airway inflammation provokes phenotypic changes in the tachykinin responsiveness of nodose neurons. Bath application of substance P (SP; 0.1 to 10 microM) to nodose neurons isolated from guinea pigs with normal uninflamed airways did not elicit measurable changes in resting electrophysiological properties. In sharp contrast, 80% of nodose neurons isolated 24 h after in vivo aerosolized antigen challenge of the airway were depolarized by 100 nM SP. Inhalation of a nonantigenic protein did not evoke the expression of SP responses. Pharmacological analysis revealed that SP responses unmasked by airway inflammation were mediated by neurokinin-2 (NK-2) tachykinin receptors. There are several potential mechanisms for transduction of an "unmasking signal" from the inflamed airway to vagal afferent somata. The vagus nerve may relay the signal, either through anterograde transport and/or nerve impulse activity. Alternatively, a signal generated by airway inflammation may be carried by the circulation to the nodose ganglia. Unilateral vagotomy significantly reduced the percentage of SP-responsive neurons compared with intact controls, suggesting that the vagus nerve is required for unmasking of NK-2 responses.
Moore
K A
KA
Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore 21201-1559, USA.
Undem
B J
BJ
Weinreich
D
D
D000818:Animals; D000941:Antigens / Q000008:administration & dosage*; D001549:Benzamides / Q000494:pharmacology; D004195:Disease Models, Animal; D006168:Guinea Pigs; D008297:Male; D008564:Membrane Potentials; D008855:Microscopy, Electron, Scanning; D064729:Neurokinin-1 Receptor Antagonists; D010047:Ovalbumin / Q000008:administration & dosage*; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013373:Substance P / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects / Q000294:innervation* / Q000648:ultrastructure; D014136:Tracheitis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D014628:Vagotomy; D014630:Vagus Nerve / Q000187:drug effects / Q000378:metabolism* / Q000601:surgery
D000941:Antigens; D001549:Benzamides; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; C080755:3-(2-methoxybenzylamino)-2-phenylpiperidine; D013373:Substance P; C073839:SR 48968; D010047:Ovalbumin