Substance P and neurokinin-1 receptor expression by intrinsic airway neurons in the rat

J. Julio Pérez Fontán, Daniel N. Cortright, James E. Krause, Christine R. Velloff, Vladimir V. Karpitskyi, Terry W. Carver, Steven D. Shapiro, Bassem N. Mora

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36 Scopus citations

Abstract

Tachykinins and their receptors are involved in the amplification of inflammation in the airways. We analyzed the expression of preprotachykinin- A (PPT-A) and neurokinin-1 (NK-1) receptor genes by intrinsic airway neurons in the rat. We also tested the hypothesis that PPT-A-encoded peptides released by these neurons fulfill the requisite role of substance P in immune complex injury of the lungs. We found that ganglion neurons in intact and denervated airways or in primary culture coexpress PPT-A and NK-1 receptor mRNAs and their protein products. Denervated ganglia from tracheal xenografts (nu/nu mice) or syngeneic lung grafts had increased PPT-A mRNA contents, suggesting preganglionic regulation. Formation of immune complexes in the airways induced comparable inflammatory injuries in syngeneic lung grafts, which lack peptidergic sensory fibers, and control lungs. The injury was attenuated in both cases by pretreatment with the NK-1 receptor antagonist LY-306740. We conclude that tachykinins released by ganglia act as a paracrine or autocrine signal in the airways and may contribute to NK-1 receptor-mediated amplification of immune injury in the lungs.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume278
Issue number2 22-2
Publication statusPublished - Feb 2000

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Keywords

  • Autonomic denervation
  • Parasympathetic nervous system
  • Trachea

ASJC Scopus subject areas

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

Cite this

Fontán, J. J. P., Cortright, D. N., Krause, J. E., Velloff, C. R., Karpitskyi, V. V., Carver, T. W., ... Mora, B. N. (2000). Substance P and neurokinin-1 receptor expression by intrinsic airway neurons in the rat. American Journal of Physiology - Lung Cellular and Molecular Physiology, 278(2 22-2).