Tachykinins in the lungs

Abstract

Tachykinins are neuropeptides which regulate various biological responses, some of which are potentially important in the pathogenesis of pulmonary diseases such as asthma. Tachykinins produce their biological effects by stimulating specific tachykinin receptors (NK(1), NK(2) and NK(3)). Tachykinins have a variety of effects in the lungs. They are among the most potent bronchoconstrictor agents known and have potent effects on airway blood vessel caliber, causing vasodilation by an endothelium-dependent mechanism. Exogenously administered tachykinins (substance P, neurokinin A and neurokinin B) induce mucus secretion in most species, including humans. In addition to having effects on airway secretion, tachykinins also modulate the mucociliary clearance mechanisms of the airway. Tachykinin receptors are found on pulmonary/bronchial C fibers, and both excitatory and inhibitory effects of tachykinins on neural discharge and neurotransmitter release from these nerves have been described. Tachykinins are also involved in several reflex responses, particularly the cough reflex. Tachykinins have been implicated in the inflammatory response in the lungs and they also participate in the regulation of the immune system. A considerable body of evidence implicates tachykinins as important mediators of the neurogenic inflammatory response in a variety of pulmonary diseases. It is thus expected that tachykinin receptor antagonists will prove useful in the therapy of diseases such as asthma, allergic rhinitis and chronic bronchitis.