Gn. Colasurdo et al., MODULATION OF ACETYLCHOLINE-RELEASE IN RABBIT AIRWAYS IN-VITRO, American journal of physiology. Lung cellular and molecular physiology, 12(3), 1995, pp. 432-437
We investigated the effects of substance P (SP) and vasoactive intesti
nal peptide (VIP) on acetylcholine (ACh) released from nerve endings b
y electrical field stimulation (EFS) in rabbit airways in vitro. ACh r
elease was directly measured using highperformance liquid chromatograp
hy with electrochemical detection. Airway smooth muscle (ASM) segments
, dissected from the midtrachea down to the left mainstem bronchus, we
re obtained from New Zealand White rabbits and mounted in organ baths
containing modified Krebs-Henseleit solution, physostigmine, and choli
ne. EFS at 20 Hz was delivered for 15 min to define baseline ACh relea
se (pmol per gram of tissue per minute). There were no significant reg
ional differences in ACh release during these baseline studies. A seco
nd stimulation was then performed in the absence (control) and presenc
e of one or more of the following substances: SP (10(-7) M), a nonpept
ide antagonist of the NK1 receptor (10(-7) M CP-96,345; Pfizer), and V
IP (10(-7) M). Results for ACh release are expressed as a percentage o
f 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 decrea
sed SP-induced ACh release in all ASM segments. We conclude that SP si
gnificantly increases ACh release, thus facilitating cholinergic neuro
transmission; its effect is abolished by CP-96,345. VIP decreases SP-i
nduced ACh release, indicating a modulatory effect on cholinergic neur
otransmission.