Na+,K(+)-ATPase activity in CNS and noradrenergic neurotransmission: time course of differential desipramine (DMI) effects.
ATPase activities in CNS membranes were studied after administration of desipramine (DMI), a noradrenaline (NA) uptake inhibitor. In a previous paper we reported that Na+,K(+)-ATPase activity significantly increased 3 h after DMI administration (10 mg/kg) in hypothalamus and mesencephalus but not in cerebral cortex and pons-medulla oblongata membranes (Viola et al., Cell. molec. Neurobiol. 1989, 9, 263-271). Here it was observed that Na+,K(+)-ATPase increase induced by acute DMI disappeared at 24 h in hypothalamus but remained during 21 days in mesencephalus. Na+,K(+)-ATPase increase by acute DMI was inhibited when endogenous NA was depleted by the noradrenergic neurotoxin DSP-4 or the NA synthesis inhibitor alpha-methyl-p-tyrosine. On the whole, Mg(2+)-ATPase activity was not modified by treatment. 5'-nucleotidase, another membrane-bound enzyme, was unchanged by acute DMI. The addition of DMI in vitro (50 ng/mg tissue) during Na+,K(+)-ATPase assay failed to affect ATPase activities. Acute DMI effects on Na+,K(+)-ATPase are thus attributable to noradrenergic neurotransmission rather than to non-specific drug-CNS membrane interaction. Furthermore, DMI produces differential effects on membrane Na+,K(+)-ATPase, depending on treatment conditions and CNS area studied.
Viola
M S
MS
Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
Rodríguez de Lores Arnaiz
G
G
Enero
M A
MA
D015720:5'-Nucleotidase / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000201:enzymology*; D002540:Cerebral Cortex / Q000201:enzymology; D003891:Desipramine / Q000494:pharmacology*; D005260:Female; D007031:Hypothalamus / Q000201:enzymology; D007700:Kinetics; D008297:Male; D008526:Medulla Oblongata / Q000201:enzymology; D008636:Mesencephalon / Q000201:enzymology; D009638:Norepinephrine / Q000502:physiology*; D011149:Pons / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*
D015720:5'-Nucleotidase; D000254:Sodium-Potassium-Exchanging ATPase; D003891:Desipramine; D009638:Norepinephrine