Calcium-sensitive accumulation of norepinephrine in rat cerebral cortex.
The accumulation of high and low concentrations of [3H]-norepinephrine has been examined in a crude synaptosomal preparation of rat cerebral cortex in the presence and absence of uptake1 inhibitors. When uptake1 was blocked, [3H]-norepinephrine accumulation exhibited very rapid initial rates. It was not inhibited by 10 mM normetanephrine, a potent inhibitor of peripheral uptake2, but it was inhibited by 10 mM metaraminol. This accumulation was markedly reduced when calcium ions were omitted from the incubation medium, and is named here 'calcium-sensitive accumulation' (CSA) to distinguish it functionally from the sodium-dependent, high affinity, uptake1 process. CSA may be localized in nerve endings since it was found predominantly i the synaptosomal fraction of homogenates subjected to density gradient centrifugation in sucrose or in Ficoll-in-sucrose. At high concentrations of [3H]l-norepinephrine (1.0 microM) and short incubation times, CSA accounted for most of the total accumulation of [3H]l-norepinephrine whereas uptake1 contributed only a small portion. Since extracellular concentrations of brain norepinephrine are thought to reach levels in excess of 1.0 microM, CSA may be a significant factor in noradrenergic neuronal transmission.
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000502:physiology*; D003891:Desipramine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008680:Metaraminol / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D009647:Normetanephrine / Q000494:pharmacology; D051381:Rats; D013347:Subcellular Fractions / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism; D013997:Time Factors
D009647:Normetanephrine; D008680:Metaraminol; D002118:Calcium; D003891:Desipramine; D009638:Norepinephrine