Non-adrenergic, non-cholinergic neural control of the airways.
1. In addition to the classical cholinergic bronchoconstrictor and adrenergic bronchodilator neural mechanisms, there is a large volume of evidence to suggest the existence of neural pathways within the airways of a variety of species which are neither adrenergic nor cholinergic, the non-adrenergic, non-cholinergic (NANC) mechanisms. With respect to airway smooth muscle tone, NANC neural responses may induce either contraction (excitatory, e-NANC) or relaxation (inhibitory, i-NANC). Early investigations of NANC mechanisms in both human and other animal airways suggested a role for neuropeptides as the putative neurotransmitters. 2. Excitatory NANC (e-NANC) bronchoconstrictor responses are believed to be mediated by the release of sensory neuropeptides from a subpopulation of non-myelinated C-fibre primary afferent neurones in the airways. e-NANC nerves, which release tachykinins such as substance P (SP), neurokinin A (NKA) and the peptide calcitonin gene-related peptide (CGRP, produced as a result of alternative splicing of the calcitonin gene) are selectively degenerated by the nerve toxin capsaicin (an extract from hot peppers), with the subsequent abolition of the e-NANC responses. Tachykinin receptors have been detected by radio-ligand receptor binding studies and visualized by autoradiographic mapping, and exogenous addition of these peptides elicits a bronchoconstrictor response in both human and other animal airways. In addition to these effects on airway smooth muscle tone, tachykinins produce an increase in microvascular permeability (and associated oedema formation), mucus hypersecretion and cause an exaggerated cholinergic bronchoconstrictor response. Thus, tachykinins may play a role in the inflammatory process and contribute to the neurogenic inflammation as seen in asthma.(ABSTRACT TRUNCATED AT 250 WORDS)
Stretton
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D000818:Animals; D001980:Bronchi / Q000294:innervation*; D006801:Humans; D009434:Neural Pathways / Q000502:physiology*; D009475:Neurons, Afferent / Q000502:physiology; D010275:Parasympathetic Nervous System / Q000502:physiology; D013564:Sympathetic Nervous System / Q000502:physiology; D014132:Trachea / Q000294:innervation*