Effect of 2-(4-phenylpiperidino)cyclohexanol on acetylcholine release and subcellular distribution in rat striatal...

These experiments measured the effect of 2-(4-phenylpiperidino)cyclohexanol (AH5183) on the release of acetylcholine (ACh) and its subcellular distribution in slices of rat striatum incubated in vitro. The AH5183, a drug that blocks the uptake of ACh by isolated synaptic vesicles, reduced the release of ACh from slices stimulated to release transmitter in response to K+ depolarization. Tissue stimulated in the presence of AH5183 contained more ACh in a nerve terminal cytoplasmic fraction than did tissue stimulated in the drug's absence, but stimulation in AH5183's presence reduced the amount of ACh measured in fractions containing synaptic vesicles. The depletion of ACh caused by stimulating tissue in the presence of AH5183 was more evident in the fraction of nerve terminal ACh occluded within synaptic vesicles as isolated by gradient centrifugation (fraction D) than it was in other nerve terminal occluded stores. It is concluded that the synaptic vesicles isolated as fraction D under the present experimental conditions likely contain releasable transmitter. The AH5183 also depressed the spontaneous release of ACh from incubated slices of striatum and this effect was evident in the presence or the absence of medium Ca2+. It is suggested that this effect might indicate that the process of spontaneous ACh release measured neurochemically results, in part, from an AH5183-sensitive carrier-mediated process.