Calcium-sensitive accumulation of norepinephrine in rat cerebral cortex

Abstract

The accumulation of high and low concentrations of [ 3H]l-norepinephrine has been examined in a crude synaptosomal preparation of rat cerebral cortex in the presence and absence of uptake 1 inhibitors. When uptake 1 was blocked, [ 3H]l-norepinephrine accumulation exhibited very rapid initial rates. It was not inhibited by 10 mM normetanephrine, a potent inhibitor of peripheral uptake 2, 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, uptake 1 process. CSA may be localized in nerve endings since it was found predominantly in the synaptosomal fraction of homogenates subjected to density gradient centrifugation in sucrose or Fn Ficoll-in-sucrose. At high concentration of [ 3H]l-norepinephrine (1.0 μM) and short incubation times, CSA accounted for most of the total accumulation of [ 3H]l-norepinephrine whereas uptake 1 contributed only a small portion. Since extracellular concentrations of brain norepinephrine are thought to reach levels in excess of 1.0 μM, CSA may be a significant factor in noradrenergic neuronal transmission.