Neurokinin receptors subserving airways secretion.

Mucus secretion can be induced in the airways by activation of nerves. The principal mechanism mediating neurogenic mucus secretion is cholinergic. However, a small but significant secretory response remains after adrenoceptor and cholinoceptor blockade. The identity of this nonadrenergic, noncholinergic (NANC) neural mechanism is unclear but includes an orthodromic pathway and a capsaicin-sensitive "sensory-efferent" (or "local effector") pathway. The orthodromic pathway comprises cholinergic nerves (and to a much lesser extent adrenergic nerves) in which neuropeptides, including vasoactive intestinal peptide (VIP) and neuropeptide tyrosine (NPY), are colocalised and coreleased with the classical neurotransmitter. Investigation of the contribution of the orthodromic neural pathway to neurogenic secretion awaits development of selective receptor antagonists for VIP and NPY. The neurotransmitters of the sensory-efferent neural pathway include calcitonin gene related peptide and the tachykinin receptor agonists indicates that the tachykinin NK1 receptor is ubiquitous for airway secretory processes, including mucus secretion and ion transport. Antagonist studies show that the great proportion of the NANC neural mucus secretory response is mediated via NK1 receptors, with little or no contribution from NK2 receptors. The relevance of the sensory-efferent neural pathway in health is equivocal, but it may have increasing importance in chronic inflammatory bronchial diseases associated with mucus hypersecretion, for example, asthma and chronic bronchitis, in which there is some evidence for the potential for increased sensory-efferent neural activity.