Amiloride inhibits the vasopressin-induced increase in epithelial water permeability.
The vasopressin (VP)-induced increase in water permeability in high-resistance, amphibian epithelia is not altered by the abolition of net Na+ flux caused by amiloride added to the apical bathing medium. In this work we looked at the effects on water transport of amiloride added to the serosal medium at a concentration (10(-3) M) known to inhibit Na+/H+ exchange. In urinary bladders of Bufo marinus, amiloride partially blocked the hydrosmotic response to VP. A similar inhibition was found with cyclic adenosine 5'-monophosphate (cAMP) or serosal hypertonicity. We hypothesized that this effect of amiloride could be due to an inhibition of Na+/H+ and/or Na+/Ca2+ antiporters present in the epithelial basolateral membrane and looked at the effects of the diuretic in Na(+)-free media. A similar degree of inhibition of water flow was still found, thus showing that amiloride acts on a cell target other than the antiporters. In toad skin, amiloride did not inhibit the hydrosmotic response to VP and to isoproterenol; however the response to high K+ was significantly reduced. Among the amiloride cell targets described so far, adenylate cyclase and protein kinase A appear to be the best candidates to explain the inhibition of the hydrosmotic response reported here. Direct measurements of intracellular cAMP are needed however to substantiate this hypothesis.
Grosso
A
A
Department of Physiology, Centre Médical Universitaire (CMU), Geneva, Switzerland.
Cragoe
E J
EJ
DeSousa
R C
RC
D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D001834:Body Water / Q000378:metabolism; D002024:Bufo marinus; D000242:Cyclic AMP / Q000378:metabolism; D006982:Hypertonic Solutions; D007545:Isoproterenol / Q000494:pharmacology; D009994:Osmolar Concentration; D011189:Potassium Chloride / Q000494:pharmacology; D012869:Skin Absorption / Q000187:drug effects*; D012964:Sodium / Q000378:metabolism; D014667:Vasopressins / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D006982:Hypertonic Solutions; D014667:Vasopressins; D011189:Potassium Chloride; D000584:Amiloride; D012964:Sodium; D000242:Cyclic AMP; D007545:Isoproterenol