G-protein coupled receptors regulating cough

Cough is a protective mechanism but can occur excessively in disease. Cough can be modulated by a range of GPCRs which can be either inhibitory or excitatory. Prostaglandin E2 and bradykinin can activate airway sensory nerves via EP3 and B2 receptors receptively and have both been shown to mediate their effects though TRPV1 and TRPA1 receptors. Activation of the β2-adrenoceptor and cannabinoid CB2 receptors can inhibit sensory nerves and prevent cough. It is currently thought that activation of the β2-adrenoceptor causes c-AMP dependent activation of PKA; however, recent research has suggested that the pathway involves PKG-mediated opening of the BKCa channel leading to hyperpolarization.

► PGE2 and bradykinin activate sensory nerves and evoke cough via the activation of EP3 and B2 receptors respectively. ► EP3 and B2 receptors mediate excitation via the TRPV1 and TRPA1 channels. ► Activation of the β2-adrenoceptor and the CB2 receptor inhibit vagal sensory nerve activity and the cough reflex. ► β2-adrenoceptor agonists hyperpolarise the nerve via a PKG/BKCa pathway leading to an inhibition of sensory nerve activation and cough.