AJP - Lung Cellular and Molecular Physiology, Vol 268, Issue 3 432-L437, Copyright © 1995 by American Physiological Society
Modulation of acetylcholine release in rabbit airways in vitro
G. N. Colasurdo, J. E. Loader, J. P. Graves and G. L. Larsen
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, University of Colorado School of Medicine, Denver 80206.
We investigated the effects of substance P (SP) and vasoactive intestinal
peptide (VIP) on acetylcholine (ACh) released from nerve endings by
electrical field stimulation (EFS) in rabbit airways in vitro. ACh release
was directly measured using high-performance liquid chromatography with
electrochemical detection. Airway smooth muscle (ASM) segments, dissected
from the midtrachea down to the left mainstem bronchus, were obtained from
New Zealand White rabbits and mounted in organ baths containing modified
Krebs-Henseleit solution, physostigmine, and choline. EFS at 20 Hz was
delivered for 15 min to define baseline ACh release (pmol per gram of
tissue per minute). There were no significant regional differences in ACh
release during these baseline studies. A second stimulation was then
performed in the absence (control) and presence of one or more of the
following substances: SP (10(-7) M), a nonpeptide antagonist of the NK1
receptor (10(-7) M CP-96,345; Pfizer), and VIP (10(-7) M). Results for ACh
release are expressed as a percentage of the first stimulation (means +/-
SE). SP significantly increased ACh release in all ASM segments. This
effect was abolished by CP-96,345. VIP alone did not affect ACh release.
However, it significantly decreased SP-induced ACh release in all ASM
segments. We conclude that SP significantly increases ACh release, thus
facilitating cholinergic neurotransmission; its effect is abolished by
CP-96,345. VIP decreases SP-induced ACh release, indicating a modulatory
effect on cholinergic neurotransmission.
