Possible role of sialocompounds in the uptake of choline into synaptosomes and nerve cell cultures.
Incubation of primary nerve cell cultures and of crude synaptosomal preparations with neuraminidase released sialic acid from both gangliosides and sialoglycoproteins. After this treatment, the pattern of ganglioside distribution was severely modified with a decrease of polysialogangliosides (GD1b, GT1b, Gt1L, GQ1) and a dramatic increase in monosialoganglioside GM1. The choline influx into neuraminidase treated cells and organelles was reduced by 30--50% but the efflux was unmodified. In particular the high affinity mechanism of choline uptake disappeared and the low affinity mechanism was modified in both cases. The disappearance of the high affinity uptake mechanism was not followed by a decreased acetylcholine synthesis as it should be if the current theories on choline uptake and acetylcholine synthesis are correct. Our present data thus confirm our previous hypothesis that choline metabolism regulates choline uptake rather than the other way round as is suggested by the theories most widely accepted at present. Choline uptake was unaffected by pretreatment of cells and organelles with tetanus toxin suggesting that the effect of neuraminidase on the choline uptake were either mediated through glycoproteins or through gangliosides other than those which bind to tetanus toxin (GD1b and GT1b). Several speculative models for explaining the effect of neuraminidase on choline uptake are proposed.
D000818:Animals; D001921:Brain / Q000166:cytology; D002460:Cell Line; D002642:Chick Embryo; D002794:Choline / Q000378:metabolism*; D005732:Gangliosides / Q000502:physiology; D006023:Glycoproteins / Q000502:physiology; D007700:Kinetics; D009439:Neuraminidase / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D012794:Sialic Acids / Q000502:physiology*; D013574:Synaptosomes / Q000378:metabolism*
D005732:Gangliosides; D006023:Glycoproteins; D012794:Sialic Acids; D009439:Neuraminidase; D002794:Choline