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 language | English (US) |
|---|---|
| Pages (from-to) | 899-902 |
| Number of pages | 4 |
| Journal | American Review of Respiratory Disease |
| Volume | 137 |
| Issue number | 4 |
| State | Published - 1988 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
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Stimulation of Cl secretion by neurokinin A and neurokinin B in canine tracheal epithelium. / Tamaoki, J.; Ueki, I. F.; Widdicombe, Jonathan; Nadel, J. A.
In: American Review of Respiratory Disease, Vol. 137, No. 4, 1988, p. 899-902.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Stimulation of Cl secretion by neurokinin A and neurokinin B in canine tracheal epithelium
AU - Tamaoki, J.
AU - Ueki, I. F.
AU - Widdicombe, Jonathan
AU - Nadel, J. A.
PY - 1988
Y1 - 1988
N2 - 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.
AB - 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.
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M3 - Article
C2 - 2833141
AN - SCOPUS:0023918299
VL - 137
SP - 899
EP - 902
JO - American Journal of Respiratory and Critical Care Medicine
JF - American Journal of Respiratory and Critical Care Medicine
SN - 1073-449X
IS - 4
ER -