Inhibition of Na-K-Cl cotransport by amiloride analogues is associated with stimulation of cyclic AMP-dependent protein kinase.
Analogues of amiloride are widely used as pharmacological probes for inhibition of sodium-hydrogen counter-transport. In Jurkat cells, a leukemic T lymphocyte cell line, analogues of amiloride are also potent inhibitors of Na-K-Cl cotransport. The effects of these agents are not additive with those of beta-adrenoceptor agonists (which inhibit Na-K-Cl cotransport presumably by stimulation of adenylyl cyclase). Further, analogues of amiloride potently stimulate cAMP-dependent protein kinase activity. The present studies indicate that beta-adrenoceptor agonists and analogues of amiloride both act to inhibit Na-K-Cl cotransport and both stimulate cAMP-dependent protein kinase activity. Furthermore, these studies demonstrate a novel mechanism by which amiloride analogues may mediate effects separately from inhibition of sodium-hydrogen exchange.
Feldman
R D
RD
Department of Medicine, University of Western Ontario, London, Canada.
Dixon
S J
SJ
D000262:Adenylyl Cyclases / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology; D001693:Biological Transport, Active / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism*; D002713:Chlorine / Q000378:metabolism*; D003600:Cytosol; D006801:Humans; D006863:Hydrogen-Ion Concentration; D011188:Potassium / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D012413:Rubidium / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012964:Sodium / Q000378:metabolism*; D028021:Sodium-Potassium-Chloride Symporters; D014407:Tumor Cells, Cultured
D000318:Adrenergic beta-Agonists; D002352:Carrier Proteins; D028021:Sodium-Potassium-Chloride Symporters; D002713:Chlorine; D000584:Amiloride; D012964:Sodium; D011494:Protein Kinases; D000262:Adenylyl Cyclases; D012413:Rubidium; D011188:Potassium