Stereospecificity of high- and low-affinity transport of choline analogues into rat cortical synaptosomes.
The present experiments used methylcholines to examine the stereoselectivity of choline transport into rat synaptosomes. R(+)-alpha-methylcholine and S(+)-beta-methylcholine were significantly better inhibitors of the high-affinity choline transport system than were their enantiomers. Although both enantiomers of alpha- and of beta-methylcholine inhibited [3H]choline transport, only R(+)-alpha-methylcholine and S(+)-beta-methylcholine could be transported by the high-affinity choline uptake mechanism. Therefore, we conclude that the chiral requirements for recognition of and for transport by the high-affinity transporter are clearly different. In addition to high-affinity choline transport, Na(+)-independent low-affinity transport was measured. This process transported R(+)-alpha-methylcholine, but not S(-)-alpha-methylcholine; however, it showed no stereoselectivity for the enantiomers of beta-methylcholine. Thus, high- and low-affinity choline transport mechanisms exhibit distinct differences in their substrate selectivities. We suggest that the stereoselective properties of choline transport might present a unique opportunity to study choline uptake and metabolism.
Ferguson
S S
SS
Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada.
Diksic
M
M
Collier
B
B
D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002458:Cell Fractionation; D002540:Cerebral Cortex / Q000378:metabolism* / Q000502:physiology; D002794:Choline / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000494:pharmacology; D013574:Synaptosomes / Q000378:metabolism* / Q000502:physiology; D014316:Tritium
C017506:methylcholine; D014316:Tritium; D012964:Sodium; D002794:Choline