Abstract
The cardioactive drug AR-L 57 [6-(2,4-dimethoxyphenyl)-imidazo-(4,5-β)-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.
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.
- Copyright © 1980 by The American Society for Pharmacology and Experimental Therapeutics
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