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

Background and Purpose

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.

Experimental Approach

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.

Key Results

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.

Conclusions and Implications

These findings suggest that activation of either peripheral or central adenosine A₁ receptors inhibits citric acid‐induced cough and airway obstruction. The data also suggest that tonic activation of central adenosine A₁ receptors serves as a negative regulator of cough and airway obstruction, secondary to inhibition of excitatory glutamatergic and tachykininergic neurotransmission.

DOI: 10.1111/bph.14360

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