Vesicular and juxtavesicular serotonin: effects of lysergic acid diethylamide and reserpine.
An extensive analysis of subcellular serotonin (5-HT) compartmentation with and without reserpine was undertaken in order to localize further the effect of LSD on rat brain 5-HT. Modification of the subfractionation procedure resulted in an increase in purity of fractions and a decrease in variability of 5-HT content. With the modified procedure, the administration of LSD produced a significant increase in 5-HT in the nerve-ending fraction prepared from rat whole brain. LSD caused a 50% increase in 5-HT in the vesicular fraction which was recovered after osmotic disruption of nerve-endings. The increase of 5-HT in the vesicular fraction after LSD was not demonstrable in rats treated with reserpine for as long as 2 weeks postreserpine. Instead, with reserpine pretreatment the LSD-induced increase in 5-HT was localized to the intrasynaptosomally derived "end supernatant" as early as 48 hours postreserpine. Thus, an unanticipated "juxtavesicular" site capable of 5-HT retention or binding was detected. In crude subcellular fractions, by contrast, significant increase in 5-HT were not observed with LSD administration until 4 days after reserpine, at which time at least a 50% 5-HT repletion had occurred. This study of drug interactions suggests a juxtavesicular compartment that may be of functional importance in presynaptic binding or transport of 5-HT.
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000648:ultrastructure; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004347:Drug Interactions; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology*; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D012110:Reserpine / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism*; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism*
D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D012110:Reserpine; D008238:Lysergic Acid Diethylamide; D002795:Choline O-Acetyltransferase