Tachykinin NK3 and NK1 receptor activation elicits secretion from porcine airway submucosal glands
JE Phillips, JA Hey, MR Corboz - British journal of …, 2003 - Wiley Online Library
JE Phillips, JA Hey, MR Corboz
British journal of pharmacology, 2003•Wiley Online LibraryWe presently characterized the tachykinin receptor subtypes, using tachykinin receptor
agonists and selective antagonists, that induce submucosal gland fluid flux (JG) from
porcine tracheal explants with the hillocks technique. We also investigated the effects of the
tachykinin receptor agonists on the electrophysiologic parameters of the tracheal epithelium
in Ussing chambers. The NK1 tachykinin receptor agonist substance P (SP, 1 μm) and the
NK3 tachykinin receptor agonist [MePhe7] neurokinin B ([MePhe7] NKB, 1 μm) induced …
agonists and selective antagonists, that induce submucosal gland fluid flux (JG) from
porcine tracheal explants with the hillocks technique. We also investigated the effects of the
tachykinin receptor agonists on the electrophysiologic parameters of the tracheal epithelium
in Ussing chambers. The NK1 tachykinin receptor agonist substance P (SP, 1 μm) and the
NK3 tachykinin receptor agonist [MePhe7] neurokinin B ([MePhe7] NKB, 1 μm) induced …
- We presently characterized the tachykinin receptor subtypes, using tachykinin receptor agonists and selective antagonists, that induce submucosal gland fluid flux (JG) from porcine tracheal explants with the hillocks technique. We also investigated the effects of the tachykinin receptor agonists on the electrophysiologic parameters of the tracheal epithelium in Ussing chambers.
- The NK1 tachykinin receptor agonist substance P (SP, 1 μM) and the NK3 tachykinin receptor agonist [MePhe7]neurokinin B ([MePhe7]NKB, 1 μM) induced gland fluid fluxes of 0.29±0.03 μl min−1 cm−2 (n=26) and 0.36±0.05 μl min−1 cm−2 (n=24), respectively; while the NK2 tachykinin receptor agonist [βAla8]neurokinin A (4‐10) ([βAla8]NKA (4‐10), 1 μM) had no effect on JG (n=10).
- The NK1 receptor antagonist CP99994 (1 μM, n=9) blocked 93% of the SP‐induced JG, whereas the NK3 receptor antagonist SB223412 (1 μM, n=12) had no effect on the SP‐induced JG. However, SB223412 (1 μM, n=9) blocked 89% of the [MePhe7]NKB‐induced JG while CP99994 (1 μM, n=10) did not affect the [MePhe7]NKB‐induced JG. The NK2 receptor antagonist SR48968 (1 μM) did not block the JG induced by either the NK1 (n=4) or NK3 (n=13) receptor agonists.
- The nicotinic ganglionic acetylcholine receptor antagonist hexamethonium (1 μM) and the muscarinic acetylcholine receptor antagonist atropine (1 μM) also decreased the NK3 receptor agonist‐induced JG by 67% (n=10) and 71% (n=12), respectively.
- The potential difference (PD), short‐circuit current (ISC), and membrane resistance (RM) of the porcine tracheal epithelial membranes were not significantly affected by any of the neurokinin agonists or antagonists (1 μM, basolateral) used in this study, although SP and [βAla8]NKA (4‐10) induced a slight transient epithelial hyperpolarization.
- These data suggest that NK1 and NK3 receptors induce porcine airway gland secretion by different mechanisms and that the NK3 receptor agonists induced secretion is likely due to activation of prejunctional NK3 receptors on parasympathetic nerves, resulting in acetylcholine‐release. We conclude that tachykinin receptor antagonists may have therapeutic potential in diseases with pathophysiological mucus hypersecretion such as asthma and chronic bronchitis.
British Journal of Pharmacology (2003) 138, 254–260. doi:10.1038/sj.bjp.0705029
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