The Effects of Neurokinin A and Calcitonin Gene-Related Peptide on Mucociliary Activity

Abstract

Short-term exposure to airway irritants such as cigarette smoke and ammonia vapour rapidly increases the mucociliary (m.c.) activity in the rabbit maxillary sinus (1,2). These irritants are known to stimulate airway C fibres (3), and it is possible that there is a m.c. defense mechanism in the mucous membrane of the rabbit maxillary sinus mediated by C fibres. Part of the increased m.c. activity is mediated by cholinergic pathways since the response is suppressed by pretreatment with atropine or hexamethonium. It is known that parasympathomimetic drugs such as methacholine accelerate m.c. activity and transport (4,5). However, a m.c. response to C fibre stimulation remains in atropinized animals as evidenced from experiments with capsaicin, antidromic nerve stimulation and airway irritants (1,2,6,7). Thisnon-cholinergic response is mimicked by i.a. injections of substance P (SP) (8). The effect of SP is resistant to both atropine and hexamethonium, but inhibited by (D-Pr02, D-Trp7,9)SP (9). Moreover, the m.c. response to C fibre stimulation is inhibited by pretreatment with capsaicin (13 mg i.a.) or (D-Pro2, D-Trp7,9)SP (1,2,6,7). These findings suggest the existence of a m.c. defense reflex involving capsaicin-sensitive C fibres (afferent pathway) and cholinergic effector neurones (efferent pathway). The final outcome reflects the joint release of both SP (axon reflex) and acetylcholine.