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Acute potentiating effects of tumor necrosis factor‐α (TNFα) on the responses of rat vagal pulmonary sensory neurons to capsaicin challenge
Author(s) -
Hsu Chun-Chun,
Geer Marcus,
Lin You Shuei,
Lee Lu-Yuan
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.892.3
Subject(s) - trpv1 , capsaicin , tumor necrosis factor alpha , medicine , chemistry , sensory system , inducer , proinflammatory cytokine , sensory neuron , arachidonic acid , cytokine , pharmacology , sensory nerve , endocrinology , anesthesia , transient receptor potential channel , neuroscience , inflammation , biology , central nervous system , enzyme , biochemistry , receptor , gene
TNFα is a proinflammatory cytokine, and plays an important role in the pathogenesis of allergic asthma. A recent study in our lab has demonstrated that a prolonged (24–48 h) treatment with TNFα increased the Ca 2+ influx evoked by TRPV1 activators in vagal pulmonary sensory neurons (Am J Physiol 299: 483–492, 2010). The present study was carried out to test the acute effect of transient TNFα treatment on the TRPV1 sensitivity in isolated rat pulmonary sensory neurons. Our results showed: 1) A brief treatment with a low concentration of TNFα (1.44 nM; 9 min) induced a biphasic TRPV1 hypersensitivity in these neurons: the inward current evoked by capsaicin (average concentration 100 nM; 3 s) was enhanced both immediately following the TNFα treatment (Δ=280%), and after a long delay (peak at ~90 min; Δ=382%). 2) The immediate phase of the potentiating effect of TNFα was almost completely abolished by pretreatment with a COX‐2 inhibitor, NS‐398 (10 μM; 10 min), whereas the delayed phase was only partially attenuated. 3) In contrast, the same TNFα treatment did not generate any potentiating effect on the response to ATP (0.3 – 1.0 μM) challenge in these neurons. In summary, a brief treatment with TNFα induced both immediate and delayed potentiating effects on the TRPV1 sensitivity in isolated pulmonary sensory neurons, and a production of COX‐2 arachidonic acid metabolites is probably involved in the immediate sensitizing effect of TNFα. (Supported in part by NIH grant HL96914 & NSC98‐2917‐I038‐101 fellowship from ROC)