Effects of pH changes and charge characteristics in the uptake of norepinephrine by synaptosomes of rat brain.
The pH dependence of the initial uptake of norepinephrine by rat whole brain synaptosomes was studied using short incubation times at 37 degrees C in order to examine the possible involvement of the phenolic OH group. The pH vs. uptake profile exhibits a maximum near pH 8.2 in H2O medium. When the medium was changed to 2H2O, the profile showed a shift of maximum corresponding to the pKa change of the phenolic OH group. The pH vs. uptake profile of tyramine was quite different from that of norepinephrine. These pH effects on uptake were explained as manifestations of the involvement of the phenolic OH group in the process. The amine and phenolic hydroxyl groups in norepinephrine were studied separately by employing two series of compounds structurally related to catecholamines, amphetamine-like and catechol-like, for their inhibitory effects on the uptake. The inhibitions were affected by changes in pH with changes in opposite directions found for the two series indicating the need for a positive charge in the side chain and suggesting an effect of the negative charge on the ring. These charge characteristics agreed with the pH profile observed in uptake. Consequently, the two groups with opposite charge characteristics in norepinephrine both appear to function in the uptake process.
D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D001921:Brain / Q000378:metabolism*; D002396:Catechols / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D013329:Structure-Activity Relationship; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D000662:Amphetamines; D002396:Catechols; D009638:Norepinephrine