Inhibition by amiloride of both adenylate cyclase activity and the Na+/H+ antiporter in fish erythrocytes.
In fish erythrocytes isoproterenol stimulates cellular accumulation of cyclic adenosine 3':5'-monophosphate (cyclic AMP) and produces a large increase in sodium permeability which corresponds to the activation of Na+/H+ exchanges and chloride-dependent sodium uptake. The stimulation of sodium transport by isoproterenol was reproduced by adding cyclic AMP or forskolin to the medium and was blocked by propranolol. This increase in sodium permeability was completely inhibited by amiloride at the relatively high levels (0.1-1 mM) of the diuretic required to inhibit the activity of the Na+/H+ exchanger under physiological conditions in various biological systems. It was shown that amiloride inhibited cyclic AMP accumulation. This effect, which was reversible and dose-dependent (ED50 6 X 10(-6) M-maximal effect 0.5 mM), resulted from the inhibition of the catalytic unit of adenylate cyclase. Amiloride also directly inhibited the sodium entry system but the Na transporter was less sensitive than adenylate cyclase to amiloride (ED50 6 X 10(-5) M). It appears from the data presented in this report that the inhibition of sodium permeability observed in fish erythrocytes in the presence of amiloride can result either from the effect of the diuretic on the adenylate cyclase system or from the effect on the sodium transport system, depending on the conditions in which amiloride is used. Thus, caution is required when interpreting amiloride action in terms of inhibition of specific transport processes.
D000067956:Adenylyl Cyclase Inhibitors; D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D017920:Antiporters; D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D002395:Catecholamines / Q000494:pharmacology; D002463:Cell Membrane Permeability; D000242:Cyclic AMP / Q000097:blood; D004910:Erythrocyte Membrane / Q000201:enzymology; D004912:Erythrocytes / Q000201:enzymology*; D006454:Hemoglobins / Q000378:metabolism; D066298:In Vitro Techniques; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D012964:Sodium / Q000097:blood; D014337:Trout
D000067956:Adenylyl Cyclase Inhibitors; D017920:Antiporters; D002352:Carrier Proteins; D002395:Catecholamines; D006454:Hemoglobins; D011943:Receptors, Adrenergic, beta; D000584:Amiloride; D012964:Sodium; D000242:Cyclic AMP