Molecular Pharmacology, Vol 17, 350-355, Copyright © 1980 by the American Society for Pharmacology and Experimental Therapeutics

Inhibition of the Sodium Pump in Squid Axons by the Cardioactive Drug AR-L 57

¹ Institut für Pharmakologie und Toxikologie der Technischen Universität München, D-8000 München 40, West Germany
² Department of Physiology, University of London, King’s College, London WC2R 2LS, England

The cardioactive drug AR-L 57 [6-(2,4-dimethoxyphenyl)-imidazo-(4,5-)-pyridine] causes a rapid and reversible inhibition of ouabain-sensitive Na efflux from axons of Loligo forbesi loaded with ²²Na by microinjection. The half-maximally effective concentration is 58 µM. AR-L 57 also inhibits ouabain-sensitive ⁸⁶Rb influx. Raising the external K does not diminish the degree of Na-pump inhibition by AR-L 57. AR-L 57 also inhibits the ouabain-sensitive Na—Na exchange seen in axons partially poisoned with dinitrophenol. In both Na and choline seawaters, the inhibition of ouabain-sensitive Na efflux displays similar rates of onset and similar concentration-response relationships. Injection of AR-L 57 into an axon produces only a transient inhibition of Na efflux, suggesting that AR-L 57 can cross the axolemma. The onset and extent of Na-efflux inhibition by externally applied AR-L 57 are unaltered at an external pH of 6. The results show that AR-L 57 is a Na-pump inhibitor like the cardioactive glycosides, but the lack of dependence on external Na ions suggests a difference in the molecular mode of interaction with the Na pump.

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ACKNOWLEDGMENTS We wish to thank the Director and staff of the Laboratory of the Marine Biological Association, Plymouth, for providing material and facilities for this work.