MODULATION OF ACETYLCHOLINE-RELEASE IN RABBIT AIRWAYS IN-VITRO

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.