The Distribution of Catecholamine Uptake Sites in Mouse Brain

Abstract

Uptake sites rapidly remove catecholamines from the synaptic cleft and terminate neurotransmitter action prior to recycling into storage vesicles ready for further release. These uptake sites are sodium dependent and are probably present over much of the neuron since both uptake and release of dopamine (DA) has been demonstrated in dendrites, at least in the substantia nigra. Mazindol is a potent inhibitor of catecholamine uptake and binds with a high affinity to single binding sites. Affinity for noradrenaline (NA) uptake sites is greatest (IC50 for [3H] amine uptake into synaptosomes 0.65 µM), while affinity for DA uptake sites is also high (IC50 18 µM) (Hyttel 1982). Because of the high affinity of desipramine (DMI) for noradrenergic uptake sites (IC50 0.97), but low affinity for DA uptake sites (IC50 9100) the addition of this compound may be used to distinguish between NA and DA uptake sites when using [3H] Mazindol binding. Since we and others have used [3H] Mazindol binding as a useful technique to study the effects of the neurotoxin 1-methyl-4-phenyl, 1,2,3,6 tetrahydropyridine (MPTP) on DA uptake sites in mouse brain (Donnan et al 1987, Javitch et al 1986), we have documented the regional distribution of binding to DA and NA uptake sites as a basis for further study.