The role of carbonic anhydrase inhibitors on anion permeability into ox red blood cells.
1. Organic anion permeability in ox red blood cell was measured by studying steady-state self-exchange of oxalate, chosen as a prototypical substrate of the organic anion transport system previously described; chloride self-exchange measured the inorganic anion permeability. 2. Carbonic anhydrase inhibitors of the sulphonamide class inhibit both organic anion self-exchange (A-/A-) and chloride self-exchang (CL-/CL-) although carbonic anhydrase plays no role in these exchanges. These results confirm the conclusions already published that sulphonamides can act directly on the cellular membrane as specific inhibitors of anion transport. 3. There is a correlation between the chemical structure of the sulphonamides and their capacity for inhibiting transmembrane anionic exchange. It is of significance that N-sulphamyl substitution, which abolishes the carbonic anhydrase inhibitory potency, does not destroy anionic inhibitory capacity and may even increase it. 4. For each sulphonamide the capacities for inhibiting chloride transport and oxalate transport are strictly identical. Inhibition appears non-competitive. 5. The temperature sensitivity of oxalate self-exchange is exactly the same as that of chloride self-exchange. From this, and from the nature of their inhibition by sulphonamides, it is proposed that chloride and organic anions share the same transport mechanism. 6. In the light of the present results the chloruretic action of sulphonamides in various tissues, in particular the kidney, is discussed.
D000818:Animals; D002257:Carbonic Anhydrase Inhibitors / Q000502:physiology*; D002417:Cattle; D002463:Cell Membrane Permeability / Q000187:drug effects; D002712:Chlorides / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D007474:Ion Exchange; D010070:Oxalates / Q000378:metabolism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000494:pharmacology; D013696:Temperature
D002257:Carbonic Anhydrase Inhibitors; D002712:Chlorides; D010070:Oxalates; D013449:Sulfonamides