G-protein coupled receptors regulating cough

• Published in: Current opinion in pharmacology Vol. 11; no. 3; pp. 248 - 253
• Main Authors: Maher, Sarah A, Dubuis, Eric D, Belvisi, Maria G
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.06.2011
• Subjects: Animals; bradykinin; cAMP-dependent protein kinase; cannabinoids; cough; Cough - metabolism; G-protein coupled receptors; Humans; Internal Medicine; Medical Education; nerve tissue; prostaglandins; Receptors, G-Protein-Coupled - metabolism; Sensory Receptor Cells - metabolism; Signal Transduction
• ISSN: 1471-4892; 1471-4973; 1471-4973
• DOI: 10.1016/j.coph.2011.06.005

► PGE 2 and bradykinin activate sensory nerves and evoke cough via the activation of EP 3 and B 2 receptors respectively. ► EP 3 and B 2 receptors mediate excitation via the TRPV1 and TRPA1 channels. ► Activation of the β 2-adrenoceptor and the CB 2 receptor inhibit vagal sensory nerve activity and the cough reflex. ► β 2-adrenoceptor agonists hyperpolarise the nerve via a PKG/BK Ca pathway leading to an inhibition of sensory nerve activation and 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 EP 3 and B 2 receptors receptively and have both been shown to mediate their effects though TRPV1 and TRPA1 receptors. Activation of the β 2-adrenoceptor and cannabinoid CB 2 receptors can inhibit sensory nerves and prevent cough. It is currently thought that activation of the β 2-adrenoceptor causes c-AMP dependent activation of PKA; however, recent research has suggested that the pathway involves PKG-mediated opening of the BK Ca channel leading to hyperpolarization.