Allergic inflammation in isolated vagal sensory ganglia unmasks silent NK-2 tachykinin receptors.
Neuroplastic changes in vagal afferents inflicted by allergic inflammation were examined in nodose ganglia (NG) removed from guinea pigs immunized to chick ovalbumin. In control NG neurons, substance P (SP; 0.1-10 microM) produces no discernable changes in membrane electrophysiological properties or [Ca2+]i. After exposing NG from immunized animals to the sensitizing antigen in vitro, 83% of the neurons were depolarized by 100 nM SP. SP also produces an inward current, an increase in membrane conductance, and an elevation of [Ca2+]i. Buffering [Ca2+]i with BAPTA blocked the [Ca2+]i rise and the SP depolarization, indicating that internal stores of Ca2+ are required. When protein synthesis was inhibited >96% (as determined by [3H] leucine incorporation), antigen challenge still unmasked SP responses. The SP response was maximal 30 min after antigen challenge, and it was evident for at least 8 hr in intact ganglia and for 3.5 d in isolated neurons. [beta-Ala8]Neurokinin A ([beta-Ala8]NKA; 10 nM), an NK-2 selective agonist, mimicked SP; selective NK-1 and NK-3 agonists were ineffective. The EC50 values for SP and [beta-Ala8]NKA membrane currents were 78 and 33 nM, respectively. Additionally, SR48968, an NK-2 receptor antagonist, blocked these responses. Thus, antigen challenge appears to unmask an NK-2 tachykinin receptor. These data further support the hypothesis that inflammatory mediators released during immediate hypersensitivity (allergic) reactions can produce profound effects on the excitability of sensory nerves. Unmasked NK-2 receptors may serve an excitatory autoreceptor function, provide a pathway for paracrine signaling between NG neurons, and contribute to ectopic sensory nerve activity.
Weinreich
D
D
Department of Pharmacology and Experimental Therapeutics, School of Medicine, University of Maryland, Baltimore, Maryland 21201-1559, USA.
Moore
K A
KA
Taylor
G E
GE
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D017950:Ganglia, Sensory / Q000378:metabolism*; D006168:Guinea Pigs; D006967:Hypersensitivity / Q000150:complications*; D066298:In Vitro Techniques; D008297:Male; D009443:Neuritis / Q000209:etiology* / Q000378:metabolism* / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009620:Nodose Ganglion / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D018039:Receptors, Tachykinin / Q000378:metabolism*; D013373:Substance P / Q000494:pharmacology; D014630:Vagus Nerve / Q000378:metabolism*
D018039:Receptors, Tachykinin; D013373:Substance P