AJP - Lung Cellular and Molecular Physiology, Vol 265, Issue 3 228-L233, Copyright © 1993 by American Physiological Society
Neuromodulation mediated by neurokinin-1 subtype receptors in adult rabbit airways
C. John, S. Brunner and D. T. Tanaka
Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710.
The neuromodulatory actions of Septide, a selective neurokinin-1 (NK-1)
agonist, and substance P (SP) were investigated in isolated rabbit tracheal
smooth muscle (TSM) segments. The tissues were placed in organ baths
containing modified Krebs-Ringer solution and contracted with either the
agonists or electrical field stimulation (ES) with frequencies ranging from
1 to 50 Hz. The neutral endopeptidase (NEP) inhibitor, phosphoramidon
(10(-6) M), had no significant effect on Septide-mediated contractions.
Septide-mediated contractions were augmented in the presence of
neostigmine, eliminated in the presence of atropine, and diminished in the
presence of tetrodotoxin. Both SP and Septide increased ES-induced
contractions in a dose-dependent manner. On the other hand, the presence of
both Septide and SP did not further augment this neuromodulatory action.
After NK-1 desensitization, Septide-mediated contractions were also
virtually eliminated; however, the peptide's neuromodulatory action was
unaffected. In contrast, the presence of GR-82334, a selective NK-1
antagonist, eliminated Septide's neuromodulatory activity. These findings
provide evidence that 1) NK-1 receptors facilitate both the direct release
of ACh as well as augment the release of ACh by ES and 2) the cholinergic
pathways involved with these two processes may represent different
mechanisms.
