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  • Title: Inhibitory effect of cholesteryl gamma-aminobutyrate on evoked activity in rat hippocampal slices.
    Author: Hesse GW, Shashoua VE, Jacob JN.
    Journal: Neuropharmacology; 1985 Feb; 24(2):139-46. PubMed ID: 2986031.
    Abstract:
    Cholesteryl gamma-aminobutyrate (C-G) readily crosses the blood-brain barrier and has properties that suggest that it may be a potential gamma-aminobutyric acid (GABA)-mimetic compound. The effect of this compound on the orthodromically-evoked discharge of hippocampal pyramidal cells was investigated using slices of rat hippocampus maintained in vitro. The compound produced dose-dependent inhibition of the discharge of pyramidal cells. The magnitude of the inhibitory effect was somewhat less than that produced by a similar dose of GABA, but the duration of the inhibition was prolonged by about 10-fold over that produced by GABA. The inhibition produced by cholesteryl gamma-aminobutyrate was blocked by the addition of picrotoxin to the incubation medium, and by replacement of chloride with isethionate. In addition, pretreatment of slices with the irreversible esterase inhibitor, phenylmethylsulfonylfluoride, attenuated the effects of cholesteryl gamma-aminobutyrate, but not that of GABA. These results suggest that cholesteryl gamma-aminobutyrate has GABA-like actions in the CNS, and that its activity is largely dependent upon enzymatic release of GABA from the compound by esterases present in the tissue.
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