Inhibitory effects of chemically-different 'loop' diuretics on chloride transport across the bullfrog cornea

• Published in: Acta physiologica Scandinavica 1986-06, Vol.127 (2), p.137-144
• Main Authors: ERIKSSON, Ö., WISTRAND, P. J.
• Format: Article
• Language: English
• Subjects: Animals; Biological Transport - drug effects; chloride; chloride transport; Chlorides - metabolism; cornea; Cornea - drug effects; Cornea - metabolism; cyclic AMP; Cyclic AMP - metabolism; diuretics; Diuretics - pharmacology; Hydrogen-Ion Concentration; In Vitro Techniques; Na+-K+-ATPase; prostaglandins; Rana catesbeiana; Seasons; SITS; Sodium-Potassium-Exchanging ATPase - metabolism; Stereoisomerism; stereoisomers
• ISSN: 0001-6772; 1365-201X
• DOI: 10.1111/j.1748-1716.1986.tb07886.x

Frog (Rana catesbeiam) corneas were mounted in an Ussing chamber, modified to facilitate dissection and to avoid edge damage to the epithelial tissue during mounting and measurements. When bathed in Conway solution of pH 7.4 the corneas displayed highly stable electrical properties, with a transepithelial potential difference (PD) of 16.6 ± 1.0 mV and a short‐circuit current (SCC) of 10.3 ± 0.8 μA cm‐2. The DC resistance was 2.0 ± 0.15 k. cm2 (mean ± SE, n= 45). An increase in the intracellular cyclic AMP level induced by prostaglandin E2 and by 3‐isobutyl‐i‐methylxanthine (IBMX) resulted in an increase in SCC. Ortho‐vanadate, an inhibitor of Na+‐K+‐ATPase, reduced SCC. The acidic loop diuretics furosemide, bumetanide and the le vorotatory form of indacrinone (MK‐196) reduced SCC byaboutso%at concentrations of 500,100 and 46 μM, respectively. The (–)form of MK‐196 was four times more active than the (+)form. Dimethylation of the SO2NH2 group reduced the activity of bumetanide. The basic diuretics muzolimine (Bay G 2821) and MK‐447, were found, similarly, to reduce SCC by about 50% at concentrations of 500 μM. In view of their ‘high ceiling’ type of saluretic effects in whole animals, these basic agents should therefore be classified as ‘loop’ diuretics. The effects of these structurally highly different ‘loop’ diuretics are similar in epithelia which secrete (cornea) and in those which absorb (the renal thick ascending limb of Henle's loop; TALH) chloride ions. This could indicate that they interact with the same ‘diuretic receptor’ and have a common mode of action in both types of epithelia. Moreover, their effects on chloride transport parallel their saluretic effects. Amphibian cornea should therefore be a convenient model tissue for studies of the modes of action and the structure‐activity relationships of loop diuretics.