Stimulation of Cl secretion by neurokinin A and neurokinin B in canine tracheal epithelium

J. Tamaoki, I. F. Ueki, Jonathan Widdicombe, J. A. Nadel

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

We studied the effects of neurokinin A (NKA) and neurokinin B (NKB), the mammmalian-derived tachykinins, on the electrical and ion transport properties of canine tracheal epithelium. Both tachykinins dose-dependently increased short-circuit current (Isc) when added to the mucosal (NKA: ΔI(sc)(max) = 24.2 ± 2.4 μA/cm2, K(D) = 9 nM; NKB: ΔI(sc)(max) = 14.2 ± 2.2 μA/cm2, K(D) = 32 nM) or submucosal (NKA: ΔI(sc)(max) = 10.5 ± 1.2 μA/cm2, K(D) = 45 nM; NKB: ΔI(sc)(max) = 2.2 ± 1.4 μA/cm2, K(D) = 80 nM) bath. Isc responses to mucosal addition of tachykinins consisted of transient and subsequent steady-state components, whereas submucosal addition elicited only steady-state responses. Inhibition of Cl transport with bumetanide or substitution of Cl reduced the maximal changes in Isc. In paired tissues, NKA increased net 26Cl flux toward the mucosa from 1.83 ± 0.49 to 2.71 ± 0.46 μeq·cm-2·h-1 (p < 0.05), without affecting net 22Na flux toward the submucosa. The increases in Isc induced by tachykinins were not modified by prior tissue incubation with phentolamine, propranolol, atropine, tetrodotoxin, or indomethacin, but were effectively inhibited by (D-Pro2, D-Trp7,9) substance P. The cyclic AMP (cAMP) levels in the surface epithelium were increased by the addition of NKA and NKB. These findings suggest that NKA and NKB selectively stimulate the secretion of Cl across canine tracheal epithelium, probably by acting directly on the tachykinin receptors, and that these effects are associated with the increased production of intracellular cAMP.

Original languageEnglish (US)
Pages (from-to)899-902
Number of pages4
JournalAmerican Review of Respiratory Disease
Volume137
Issue number4
StatePublished - 1988
Externally publishedYes

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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