Neurokinin subtype receptors mediating substance P contraction in immature rabbit airways.

Published

Journal Article

Two-week-old rabbit tracheal smooth muscle (TSM) and bronchial smooth muscle (BSM) segments were placed in organ baths, and isometric contractions to substance P (SP) were obtained. In the presence of phosphoramidon (PHOS), a neutral endopeptidase inhibitor, BSM segments were significantly more reactive and sensitive to SP than TSM segments. Neither neostigmine (NEO) nor atropine (ATR) eliminated these regional differences. Airway contractile responses to: 1) Senktide (NK-3 agonist); 2) neurokinin A (NKA, a NK-2 agonist); and 3) Septide (a highly selective NK-1 agonist) were separately obtained. In the presence of PHOS and NEO, Senktide was virtually inactive in both BSM and TSM. In the presence of PHOS, NEO, and ATR, NKA was equipotent in all airway segments; in contrast, the Septide response was significantly more reactive in BSM than in TSM segments. After inhibition of NK-1 activity with GR 82334, a competitive NK-1 receptor antagonist, the regional differences in SP reactivity were greatly diminished. This latter indication of a NK-1 contribution was confirmed using Septide-mediated inactivation of NK-1 receptors whereby the regional differences in airway sensitivity to SP were eliminated. These findings indicate that both endogenous neutral endopeptidase activity as well as NK-1 and NK-2 receptor influences may modulate the contractile responses to SP in immature rabbit airways.

Full Text

Duke Authors

Cited Authors

  • Kazem, E; John, C; Tanaka, DT

Published Date

  • January 1, 1996

Published In

Volume / Issue

  • 39 / 1

Start / End Page

  • 120 - 126

PubMed ID

  • 8825396

Pubmed Central ID

  • 8825396

International Standard Serial Number (ISSN)

  • 0031-3998

Digital Object Identifier (DOI)

  • 10.1203/00006450-199604001-00729

Language

  • eng

Conference Location

  • United States