Effects of some analgesics and antidepressants on the (Na + + K + )-adenosine triphosphatase from cortices of brain and kidney.

The effects of benzomorphans, tricyclic antidepressants, monoamine oxidase (MAO) inhibitors and chlorpromazine on the microsomal (Na+ + K+)-adenosine triphosphatase (ATPase) from beef cerebral cortex were studied. As a comparison, the interaction of these drugs with the corresponding enzyme from kidney cortex was also investigated. In addition to chlorpromazine, the benzomorphans and the tricyclic antidepressants inhibited the brain enzyme considerably, whereas the MAO inhibitors had little effect. The (Na+ + K+)-ATPase from kidney was not affected by the benzomorphans or MAO inhibitors, but its activity diminished in the presence of the tricyclic antidepressants and chlorpromazine. THE EXISTENCE of an (Na+ + K+)-activated adenosine triphosphatase (ATPase) in a variety of tissues is well d0cumented.l The highest activities of this enzyme were found in nervous tissue.2 The enzyme is intimately associated with membranes, but its solubilization has recently been achieved. 3 Considerable evidence indicates the involvement of this enzyme in the active transmembrane transport of Na+ and JS+.4,s Lower aliphatic alcohols, including ethanol, as well as several general depressants have been reported to inhibit the brain (Na+ + K+)-ATPase.6-g It has also been shown that the lower alcohols produced an inhibition of cation transport in brain slices.7 Inhibitory effects of imipramine on the brain microsomal (Na+ + K+)-ATPase under various experimental conditions were reported previously.lO*ll In view of the apparent interaction of general depressants with the cell membrane, including the brain (Na’ + K+)-ATPase, it was of interest to investigate the effect of drugs having analgesic or antidepressant activity on this enzyme. As a comparison, the interaction of these compounds with the (Na+ + K+)-ATPase isolated from kidney cortex was also studied. EXPERIMENTAL PROCEDURE Materials. Beef brains and kidneys were generously supplied by Standard Beef Co., Detroit, and Russell B. Slaughter House, Ypsilanti, Mich. respectively. All common chemicals were of reagent grade. The sources of drugs were: Merck (amitriptyline), Geigy (desipramine, imipramine), Smith, Kline & French (chlorpromazine, phenazocine, tranylcypromine), Winthrop (pentazocine, cyclazocine), Ciba (hydralazine)