NA-ATPASE ACTIVITY IN CNS AND NORADRENERGIC NEUROTRANSMISSION - TIME-COURSE OF DIFFERENTIAL DESIPRAMINE (DMI) EFFECTS(, K+)

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.