Role of tachykinins in asthma

The sensory neuropeptides substance P (SP) and neurokinin A (NKA) are local ized to sensory airway nerves, from which they can be released by a variety of stimuli, including allergen, ozone, or inflammatory mediators. Sensory nerves containing these peptides are relatively scarce in human airways, bu t it is becoming increasingly evident that inflammatory cells such as eosin ophils, macrophages, lymphocytes, and dendritic cells can produce the tachy kinins SP and NKA. Moreover, immune stimuli can boost the production and se cretion of SP and NKA. SP and NKA have potent effects on bronchomotor tone, airway secretions, and bronchial circulation (vasodilation and microvascul ar leakage) and on inflammatory and immune cells. Following their release, tachykinins are degraded by neutral endopeptidase (NEP) and angiotensin-con verting enzyme. The airway effects of the tachykinins are largely mediated by tachykinin NK1 and NK2 receptors. Tachykinins contract smooth muscle mai nly by interaction with NK2 receptors, while the vascular and proinflammato ry effects are mediated by the NK1 receptor. In view of their potent effect s on the airways, tachykinins have been put forward as possible mediators o f asthma, and tachykinin receptor antagonists are a potential new class of antiasthmatic medication.