Clozapine administration modifies neurotensin effect on synaptosomal membrane Na+, K+ -ATPase activity.

Na+, K+-ATPase is inhibited by neurotensin, an effect which involves the peptide high affinity receptor (NTS1). Neurotensin effect on cerebral cortex synaptosomal membrane Na+, K+-ATPase activity of rats injected i.p. with antipsychotic clozapine was studied. Whereas 3.5 x 10(-6) M neurotensin decreased 44% Na+, K+-ATPase activity in the controls, the peptide failed to modify enzyme activity 30 min after a single 3.0, 10.0 and 30.0 mg/kg clozapine dose. Neurotensin decreased Na+, K+-ATPase activity 40 or 20% 18 h after 3.0 or 5.6 mg/kg clozapine administration, respectively, and lacked inhibitory effect 18 h after 17.8 and 30.0 mg/kg clozapine doses. Results indicated that the clozapine treatment differentially modifies the further effect of neurotensin on synaptosomal membrane Na+, K+-ATPase activity according to time and dose conditions employed. Taken into account that clozapine blocks the dopaminergic D2 receptor, findings obtained favor the view of an interplay among neurotensinergic receptor, dopaminergic D2 receptor and Na+, K+-ATPase at synaptic membranes.

The inhibitory effect of neurotensin on synaptosomal membrane Na+, K+-ATPase is altered by antipsychotic administration.

Synaptosomal membrane Na+, K+-ATPase is inhibited by neurotensin, an effect which involves its high affinity receptor (NTS1) [Lopez Ordieres MG, Rodriguez de Lores Arnaiz, G. Peptides 2000; 21:571-576.]. Herein, the effect of neurotensin on synaptosomal membrane Na+, K+-ATPase of rats 18 h after i.p. administration of antipsychotic haloperidol (2 mg/kg) or clozapine (10 mg/kg) was studied. Basal enzyme activity after these treatments did not differ from that in vehicle-treated rats. It was observed that 3.5 x 10(-6) M neurotensin reduced roughly 40% cerebral cortex Na+, K+-ATPase from vehicle-injected rats, produced no effect on the enzyme from rats injected with haloperidol but enhanced 26% that from rats injected with clozapine. The peptide decreased 40% striatal Na+, K+-ATPase from vehicle-injected rats or from rats injected with clozapine, whereas it failed to alter this enzyme activity from rats injected with haloperidol. Haloperidol and clozapine (1 x 10(-6) M) added in vitro failed to alter Na+, K+-ATPase activity in cerebral cortex synaptosomal membranes. Results obtained after antipsychotic administration may well offer an alternative explanation for the particular side effects recorded in therapeutics by typical (haloperidol) versus atypical (clozapine) antipsychotic drugs.