Characterization of potent Na+/H+ exchange inhibitors from the amiloride series in A431 cells.

摘要: Na+/H+ exchange is stimulated in a variety of cell types by addition mitogenic polypeptides such as epidermal growth factor or platelet-derived factor. In order to assess the importance response, it desirable have available inhibitors this process which exhibit high affinity and good specificity. We characterize report number 5-alkylamino-substituted derivatives amiloride [3,5-diamino-6-chloro-N-(diaminomethylene)pyrazinecarboxamide++ +] show much higher than parent compound for antiporter A431 cells. High conferred substitution with two alkyl groups increased introducing branched chain. An analogue bearing 5-anilino group also very potent. These analogues effectively inhibit elevation intracellular pH upon stimulation factors. assessed other potential inhibitory effects these compounds on cellular metabolism. agreement previous reports, we find that inhibits protein synthesis both cells cell-free translation systems. While its similar inhibition system, most at lower concentrations does amiloride. are potent purified Na,K-ATPase cause profound decrease K+ well ATP content. latter effects, however, require 5-7 times those inhibiting synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)