Allergic inflammation in isolated vagal sensory ganglia unmasks silent NK-2 tachykinin receptors.

Abstract

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.

• Authors: D Weinreich, K A Moore, G E Taylor
• Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 17 Issue 20 Pg. 7683-93 (Oct 15 1997) ISSN: 0270-6474 [Print] United States
• PMID: 9315890 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Receptors, Tachykinin
• Substance P

Topics

• Animals
• Dose-Response Relationship, Drug
• Electrophysiology
• Ganglia, Sensory (metabolism)
• Guinea Pigs
• Hypersensitivity (complications)
• In Vitro Techniques
• Male
• Neuritis (etiology, metabolism, physiopathology)
• Neurons (drug effects, physiology)
• Nodose Ganglion (drug effects, pathology, physiopathology)
• Receptors, Tachykinin (metabolism)
• Substance P (pharmacology)
• Vagus Nerve (metabolism)