Central adenosine A1 receptors inhibit cough via suppression of excitatory glutamatergic and tachykininergic neurotransmission

British Journal of Pharmacology
A Z El-HashimFajer Al-Shamlan

Abstract

The adenosine A1 receptor is reported to mediate several excitatory effects in the airways and has inhibitory effects in the CNS. In this study, we investigated the role of peripheral and central A1 receptors in regulating cough and airway obstruction. Drugs were administered to guinea pigs via inhalation or i.c.v. infusion. Following the administration of different drugs, cough was induced by exposing guinea pigs to aerosolized 0.4 M citric acid. An automated analyser recorded both cough and airway obstruction simultaneously using whole-body plethysmography. The A1 receptor agonist, cyclopentyladenosine (CPA, administered by inhalation), dose-dependently inhibited cough and also inhibited airway obstruction. Similarly, CPA, administered i.c.v., inhibited both the citric acid-induced cough and airway obstruction; this was prevented by pretreatment with the A1 receptor antagonist DPCPX (i.c.v.). Treatment with DPCPX alone dose-dependently enhanced the citric acid-induced cough and airway obstruction. This effect was reversed following treatment with either the glutamate GluN1 receptor antagonist D-AP5 or the neurokinin NK1 receptor antagonist FK-888. These findings suggest that activation of either peripheral or central adenosin...Continue Reading

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Citations

Nov 18, 2020·International Journal of Molecular Sciences·Carla Trapero, Mireia Martín-Satué

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