Ms. Viola et al., NA-ATPASE ACTIVITY IN CNS AND NORADRENERGIC NEUROTRANSMISSION - TIME-COURSE OF DIFFERENTIAL DESIPRAMINE (DMI) EFFECTS(, K+), Neurochemistry international, 24(1), 1994, pp. 91-97
ATPase activities in CNS membranes were studied after administration o
f desipramine (DMI). a noradrenaline (NA) uptake inhibitor. In a previ
ous paper we reported that Na+, K+-ATPase activity significantly incre
ased 3 h after DMI administration (10 mg/kg) in hypothalamus and mesen
cephalus but not in cerebral cortex and pons-medulla oblongata membran
es (Viola et al., Cell. molec. Neurobiol. 1989, 9, 263-271). Here it w
as observed that Na+, K+-ATPase increase induced by acute DMI disappea
red at 24 h in hypothalamus but remained during 21 days in mesencephal
us. Na+, K+-ATPase increase by acute DMI was inhibited when endogenous
NA was depleted by the noradrenergic neurotoxin DSP-4 or the NA synth
esis inhibitor alpha-methyl-p-tyrosine. On the whole, Mg2+-ATPase acti
vity 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-C
NS membrane interaction. Furthermore, DMI produces differential effect
s on membrane Na+, K+-ATPase, depending on treatment conditions and CN
S area studied.