Effect of 1DMe, a neuropeptide FF analog, on acetylcholine release from myenteric plexus of guinea pig ileum

Since neuropeptide FF (NPFF) is a putative neurotransmitter to exert anti-o pioid activity, we examined the effects Of [D-Tyr(1), (NMe)Phe(3)]neuropept ide FF (1 DMe), a stable NPFF analog, on acetylcholine (ACh) release from a longitudinal muscle-myenteric plexus (LMMP) preparation of guinea pig ileu m in which opioids were known to inhibit ACh release when muscarinic autoin hibition was not fully activated. In the presence of atropine, 1 DMe increa sed spontaneous and electrical field stimulation (EFS)-evoked ACh release i n a concentration-dependent manner. Naloxone also increased ACh release. Th e stimulatory effects of 1 DMe and naloxone were not additive. In the absen ce of atropine, 1 DMe did not affect ACh release. Morphine decreased sponta neous and EFS-evoked ACh release in the presence of 1 muM atropine. 1 DMe a s well as naloxone counteracted the inhibitory effects of morphine on EFS-e voked ACh release. The combination of 1 DMe and naloxone was not more inhib itory than either drug alone. 1 DMe had no appreciable effect on norepineph rine-induced inhibition of spontaneous and EFS-evoked ACh release. These re sults first demonstrated the effects of a NPFF analog on neurotransmitter r elease: 1 DMe had a stimulatory effect on spontaneous and EFS-induced ACh r elease from the LMMP preparation of guinea pig ileum, probably by counterac ting the inhibitory effect of endogenous opioids on ACh release.