Neurokinin-neurotrophin interactions in airway smooth muscle

Lucas W. Meuchel, Alecia Stewart, Dan F. Smelter, Amard J. Abcejo, Michael A. Thompson, Syed I A Zaidi, Richard J. Martin, Y.s. Prakash

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Neurally derived tachykinins such as substance P (SP) play a key role in modulating airway contractility (especially with inflammation). Separately, the neurotrophin brainderived neurotrophic factor (BDNF; potentially derived from nerves as well as airway smooth muscle; ASM) and its tropomyosin-related kinase receptor, TrkB, are involved in enhanced airway contractility. In this study, we hypothesized that neurokinins and neurotrophins are linked in enhancing intracellular Ca2+ concentration ([Ca2+]i) regulation in ASM. In rat ASM cells, 24 h exposure to 10 nM SP significantly increased BDNF and TrkB expression (P < 0.05). Furthermore, [Ca2+]i responses to 1 μ M ACh as well as BDNF (30 min) effects on [Ca2+]i regulation were enhanced by prior SP exposure, largely via increased Ca2+ influx (P < 0.05). The enhancing effect of SP on BDNF signaling was blunted by the neurokinin-2 receptor antagonist MEN-10376 (1 M, μP < 0.05) to a greater extent than the neurokinin-1 receptor antagonist RP-67580 (5 nM). Chelation of extracellular BDNF (chimeric TrkB-Fc; 1 μg/ml), as well as tyrosine kinase inhibition (100 nM K252a), substantially blunted SP effects (P < 0.05). Overnight (24 h) exposure of ASM cells to 50% oxygen increased BDNF and TrkB expression and potentiated both SPand BDNF-induced enhancement of [Ca2+]i (P < 0.05). These results suggest a novel interaction between SP and BDNF in regulating agonistinduced [Ca2+]i regulation in ASM. The autocrine mechanism we present here represents a new area in the development of bronchoconstrictive reflex response and airway hyperreactive disorders.

Original languageEnglish (US)
Pages (from-to)91-98
Number of pages8
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume301
Issue number1
DOIs
StatePublished - Jul 2011

Fingerprint

Brain-Derived Neurotrophic Factor
Nerve Growth Factors
Smooth Muscle
Substance P
Neurokinin-2 Receptors
Neurokinin-1 Receptor Antagonists
trkB Receptor
Multiple Endocrine Neoplasia Type 1
Tachykinins
Protein-Tyrosine Kinases
Reflex
Oxygen
Inflammation

Keywords

  • Brain-derived neurotrophic factor
  • Bronchial smooth muscle
  • Calcium
  • Hyperoxia
  • Oxygen
  • Substance p
  • Tropomyosin related kinase

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology
  • Physiology

Cite this

Neurokinin-neurotrophin interactions in airway smooth muscle. / Meuchel, Lucas W.; Stewart, Alecia; Smelter, Dan F.; Abcejo, Amard J.; Thompson, Michael A.; Zaidi, Syed I A; Martin, Richard J.; Prakash, Y.s.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 301, No. 1, 07.2011, p. 91-98.

Research output: Contribution to journalArticle

Meuchel, LW, Stewart, A, Smelter, DF, Abcejo, AJ, Thompson, MA, Zaidi, SIA, Martin, RJ & Prakash, YS 2011, 'Neurokinin-neurotrophin interactions in airway smooth muscle', American Journal of Physiology - Lung Cellular and Molecular Physiology, vol. 301, no. 1, pp. 91-98. https://doi.org/10.1152/ajplung.00320.2010
Meuchel, Lucas W. ; Stewart, Alecia ; Smelter, Dan F. ; Abcejo, Amard J. ; Thompson, Michael A. ; Zaidi, Syed I A ; Martin, Richard J. ; Prakash, Y.s. / Neurokinin-neurotrophin interactions in airway smooth muscle. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2011 ; Vol. 301, No. 1. pp. 91-98.
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