Neurochemistry international
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The positive allosteric effects of four structurally distinct general anaesthetics (propofol, pentobarbitone, etomidate and 5alpha-pregnan-3alpha-ol-20-one [5alpha3alpha]) upon recombinant GABA(A) (alpha6beta3gamma2L), invertebrate GABA (RDL) and glycine (alpha1) receptors expressed in Xenopus laevis oocytes have been determined. Propofol and pentobarbitone enhanced agonist (GABA or glycine as appropriate) evoked currents at GABA(A), glycine, and RDL receptors, whereas etomidate and 5alpha3alpha were highly selective for the GABA(A) receptor. Utilizing site-directed mutagenesis, we demonstrate that the nature of the interaction of propofol, pentobarbitone and etomidate (but not 5alpha3alpha) with mammalian and invertebrate ionotropic GABA receptors depends critically upon the nature of a single amino acid located in the second transmembrane region (TM2) of these receptors. These data are discussed in relation to the specificity of action of general anaesthetics.
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We examined the effects of cytidine (5?)-diphosphocholine (CDP-choline) on plasma levels of cytidine, choline, and unchanged CDP-choline among normal volunteers receiving the substance orally or intravenously, and rats receiving it intravenously. Two hours after a single oral dose (2g), plasma choline levels were increased by 48% and plasma cytidine by 136%. Among subjects receiving three doses (2g each) at two-hour intervals, plasma choline peaked (30% over baseline) 4 h after the initial CDP-choline dose, while plasma cytidine levels continued to increase for at lest 6 h, at which time they were five times basal levels (P < 0.01). ⋯ In rats given a bolus injection of CDP-choline, five minutes earlier, the unchanged compound was also undetectable in plasma, while plasma cytidine levels increased markedly and remained elevated for at least 60 min. These observations show that CDP-choline is converted to at least two major circulating metabolites, choline and cytidine. Since both of these compounds are used in the biosynthesis of phosphatidylcholine, both may be involved in the long-term effects of the CDP-choline.