Differential effects of DSP-4 on noradrenaline axons in cerebral cortex and hypothalamus may reflect heterogeneity of noradrenaline uptake sites.
The effect of the noradrenergic neurotoxin DSP-4 on high affinity transport of noradrenaline (NAT) was studied using rat brain synaptosomes. DSP-4 decreased NAT with the characteristics of a competitive inhibitor. The neurotoxin was more potent in inhibiting NAT into cortical synaptosomes (Ki = 179 +/- 39 nM) than into hypothalamic synaptosomes (Ki = 460 +/- 35 nM). Differences in NAT into cortical and hypothalamic synaptosomes were also observed with noradrenaline itself (Km = 39.5 +/- 7.5 nM and 100 +/- 12.1 nM, respectively) and with the catecholamine uptake blocker mazindol (Ki = 0.55 +/- 0.05 nM and 0.30 +/- 0.08 nM, respectively). The differences in the pharmacological properties of the noradrenaline uptake carrier in cerebral cortex and hypothalamus may account for the differential effects of DSP-4 on noradrenergic axons in these two brain regions.
Zaczek
R
R
Neurobiology Laboratory, NIDA, Addiction Research Center, Baltimore, MD 21224.
Fritschy
J M
JM
Culp
S
S
De Souza
E B
EB
Grzanna
R
R
D000818:Animals; D001369:Axons / Q000737:chemistry / Q000187:drug effects*; D001596:Benzylamines / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000737:chemistry / Q000187:drug effects* / Q000648:ultrastructure; D007031:Hypothalamus / Q000737:chemistry / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D009498:Neurotoxins / Q000494:pharmacology*; D009638:Norepinephrine / Q000032:analysis*; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000032:analysis
D001596:Benzylamines; D009498:Neurotoxins; D011941:Receptors, Adrenergic; C012102:DSP 4; D009638:Norepinephrine