1887

Abstract

Summary

To understand better the action of guanidine and its antagonists on poliovirus replication, guanidine uptake by HeLa cells was studied. It was discovered that guanidine entered HeLa cells by at least two different mechanisms. At low concentrations (< 2 m), it was transported mostly by a carrier-mediated, saturable mechanism with an apparent affinity constant of 1·26 m-guanidine. About a third of uptake by this mechanism was sensitive to valinomycin and possibly dependent on membrane potential difference. At higher concentrations (5 to 10 m), transport was predominantly by a non-saturable, low affinity process. The carrier-mediated transport mechanism was similar to the organic cation H exchanger-mediated excretion of organic cations from the kidney, because it was inhibited by organic cations and by high [Li]. Physiological [Na] caused less but significant inhibition of guanidine uptake by HeLa cells. Approximately 20% of total uptake could not be inhibited with organic cations and was probably due to diffusion. The antiguanidine agents choline, dimethylethanolamine and tetraethylammonium, but not methionine, inhibited guanidine uptake by HeLa cells. The inhibition caused by these agents depended on their concentration and more or less paralleled their reported ability to block guanidine inhibition of poliovirus replication. Even though choline inhibited guanidine uptake it appeared to reverse this inhibition of virus replication primarily by blocking the intracellular action of guanidine. Some unexplained previous observations on the action of guanidine and its antagonists were discussed in view of the results of this study.

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1987-11-01
2022-06-27
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