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 E-2 and bradykinin can activate airway sensory nerves via EP3 and B-2 receptors receptively and have both been shown to mediate their effects though TRPV1 and TRPA1 receptors. Activation of the beta(2)-adrenoceptor and cannabinoid CB2 receptors can inhibit sensory nerves and prevent cough. It is currently thought that activation of the beta(2)-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.