Effects of polyamines on the uptake of neurotransmitters by rat brain synaptosomes

The influence of putrescine, spermidine, spermine, and some aliphatic alpha, w-diamines on the uptake spermine, and some aliphatic alpha, w-diamines on the uptake of neurotransmitters by rat forebrain synaptosomes was investigated. Choline uptake was most effectively inhibited by spermine (IC50 = 0.22 mM), less so by spermidine (IC50 = 4.0 mM), but not by putrescine (IC50 greater than 100 mM). At 10 mM, 1,3-diaminopropane, cadaverine, and 1,8-diaminooctane all inhibited choline uptake by 50% or more. Spermine and spermidine inhibited the uptake of dopamine with IC50 values of 2.7 and 2.2 mM, respectively. Putrescine was only slightly inhibitory (IC50 = 17.3 mM) and the other diamines were inactive. The uptake of gamma-aminobutyrate (GABA) was only slightly inhibited (15-40%) by the polyamines at 10 mM. With the exception of inhibition of glycine uptake by 1,8-diaminooctane (60%) and of glutamate uptake by cadaverine (35%) none of the polyamines, tested at 10 mM, affected the uptake of adenosine, glutamate, and glycine significantly. A possible modulatory role for polyamines in synaptic transmission through interaction by negatively charged groups of the synaptic membrane with the polycationic compounds is discussed.