A ROLE FOR DIVALENT CATIONS IN THE UPTAKE OF NORADRENALINE BY SYNAPTOSOMES

–The effects of divalent cations on the initial rates of noradrenaline uptake by synaptosomes were determined using Millipore filtration to terminate the reaction. The removal of either Ca²⁺ or Mg²⁺ from the incubation medium had no effect on uptake, but when both Ca²⁺ and Mg²⁺ were removed, uptake was reduced. Uptake was also diminished when Ca²⁺ was absent and 1 mm‐EGTA added to the medium. It appeared that Ca²⁺ was required for optimal uptake but that Mg²⁺ could partially substitute for Ca²⁺ in this regard. The reduction in the rate of uptake when both Ca²⁺⁰ and Mg²⁺ were absent could be rapidly and completely reversed by restoring Ca²⁺, Mg²⁺, or both Ca²⁺ and Mg²⁺ to the incubation medium. Of the divalent cations tested, Ca²⁺ and Mg²⁺, but not Mn²⁺, supported noradrenaline uptake. When the kinetics of uptake were examined, it was found that removing both Ca²⁺ and Mg²⁺ from the medium resulted in a reduction of the V_max for noradrenaline uptake. It is apparent from these results that, in addition to facilitating the release of noradrenaline from noradrenergic terminals, Ca²⁺ may also play a role in the uptake of noradrenaline by presynaptic nerve‐endings in the CNS.