Motor control of airway goblet cells and glands.
Activation of nerves increases airway mucus secretion. The mucus derives from submucosal glands and epithelial goblet cells. Depending upon species and airway level, innervation comprises parasympathetic (cholinergic), sympathetic (adrenergic) and 'sensory-efferent' pathways. In all species studied, cholinergic mechanisms predominate, particularly in human airways. Muscarinic M3 receptors on the secretory cells mediate the cholinergic response. Tachykinins (substance P and neurokinin A) mediate the sensory-efferent response, acting via tachykinin NK1 receptors. Endogenous mechanisms regulate the magnitude of neurogenic secretion, including enzymes (degrade neurotransmitters), nitric oxide (NO) and vasoactive intestinal peptide (VIP) (regulate stimulated secretion), and muscarinic M2 autoreceptors (inhibit acetylcholine release). Exogenous opioids also inhibit neurogenic secretion prejunctionally. Both VIP and opioids act by opening large conductance, calcium-activated potassium (BK(Ca)) channels. Present understanding of neural control of mucus secretion in animal airways requires translation into human data. This information should lead to rational development of drugs for bronchial diseases in which neurogenic mucus hypersecretion contributes to pathophysiology, including chronic bronchitis and asthma.
Rogers
D F
DF
Thoracic Medicine, National Heart and Lung Institute, Imperial College, Dovehouse Street, SW3 6LY, London, UK. ducan.rogers@ic.ac.uk
D000818:Animals; D005088:Exocrine Glands / Q000294:innervation / Q000502:physiology*; D020397:Goblet Cells / Q000502:physiology*; D006801:Humans; D009093:Mucus / Q000378:metabolism; D010275:Parasympathetic Nervous System / Q000502:physiology; D020545:Respiratory Mucosa / Q000166:cytology / Q000294:innervation / Q000502:physiology; D012143:Respiratory Physiological Phenomena; D012137:Respiratory System / Q000166:cytology / Q000294:innervation*; D013564:Sympathetic Nervous System / Q000502:physiology