Correlations between phospholipid methylation and neuronal catecholamine transport.
A change in the fluidity of biological membranes can be produced by methylation reactions which sequentially transfer methyl groups from phosphatidylethanolamine to phosphatidylcholine. Since the physical properties of membranes may affect the function of membrane-localized transport proteins, the accumulation of norepinephrine (NE) by rat cortical synaptosomes was examined in the presence of S-adenosylhomocysteine (AdoHcy) which inhibits the methylation of phospholipids. A concentration-related decrease in the uptake of [3H]NE was produced by AdoHcy with coincident decreases in the S-adenosylmethionine (AdoMet)-dependent transmethylation of phospholipids in neuronal membranes. A kinetic analysis for the effects of AdoHcy on the neuronal uptake of NE revealed a significant decrease in both the apparent Km and Vmax. Treatment of synaptosomes with adenosine, L-homocysteine thiolactone (HTL), and erythro-9(2-hydroxy-3-nonyl)adenine (EHNA) which leads to the synthesis of intracellular AdoHcy resulted in a decrease in the Vmax with no significant change in the Km. Adenosine or EHNA alone had no effect on NE uptake, but HTL alone significantly inhibited NE uptake. The data suggest that the processes of enzymatic methylation of membrane phospholipids and the transport of norepinephrine may be associated within neuronal membranes. Inhibiting phospholipid methylation reactions can reduce the efficiency of neurotransmitter removal and perhaps indirectly alter synaptic function.
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002540:Cerebral Cortex / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism; D008745:Methylation; D009638:Norepinephrine / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012435:S-Adenosylhomocysteine / Q000494:pharmacology*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D008563:Membrane Lipids; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010743:Phospholipids; D006710:Homocysteine; C010192:9-(2-hydroxy-3-nonyl)adenine; D012435:S-Adenosylhomocysteine; C007957:homocysteine thiolactone; D000225:Adenine; D000241:Adenosine; D009638:Norepinephrine