The voltage-gated sodium channel NaV1.8 blocker A-803467 inhibits cough in the guinea pig
| Autor: | Simona Svajdova, Yukiko Muroi, Nikoleta Pavelkova, Mariana Brozmanova, Marian Kollarik, Bradley J. Undem |
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| Rok vydání: | 2019 |
| Předmět: |
Pulmonary and Respiratory Medicine
Physiology business.industry General Neuroscience Sodium channel Pharmacology respiratory tract diseases Vagus nerve Guinea pig 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine 030228 respiratory system chemistry Capsaicin Medicine Respiratory system Receptor business Airway 030217 neurology & neurosurgery Action potential initiation |
| Zdroj: | Respiratory Physiology & Neurobiology. 270:103267 |
| ISSN: | 1569-9048 |
| Popis: | Cough in respiratory diseases is attributed to the activation of airway C-fibers by inflammation. Inflammatory mediators can act on multiple receptors expressed in airway C-fibers, nonetheless, the action potential initiation in C-fibers depends on a limited number of voltage-gated sodium channel (NaV1) subtypes. We have recently demonstrated that NaV1.8 substantially contributes to the action potential initiation in the airway C-fiber subtype implicated in cough. We therefore hypothesized that the NaV1.8 blocker A-803467 inhibits cough. We evaluated the cough evoked by the inhalation of C-fiber activator capsaicin in awake guinea pigs. Compared to vehicle, intraperitoneal or inhaled A-803467 caused 30-50% inhibition of cough at the doses that did not alter respiratory rate. We conclude that the NaV1.8 blocker A-803467 inhibits cough in a manner consistent with its action on the C-fiber nerve terminals in the airways. Targeting voltage-gated sodium channels mediating action potential initiation in airway C-fibers may offer a means of cough inhibition that is independent of the stimulus. |
| Databáze: | OpenAIRE |
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