Effects of diuretic treatment and of dietary sodium on renal binding of 3H-metolazone.
We report a series of experiments designed to determine if agents and conditions that have been reported to alter sodium reabsorption, Na-K-ATPase activity or cellular structure in the rat distal nephron might also regulate the density or affinity of binding of 3H-metolazone to the putative thiazide receptor in the distal nephron. Experimental conditions selected for study were acute (60-min) and chronic hydrochlorothiazide (HCTZ), acute acetazolamide, acute and chronic furosemide, and 14 days of varied intake of dietary sodium. The density of the binding of 3H-metolazone was increased 47% by acute HCTZ (P less than 0.001) and 39% (P less than 0.001) by acute furosemide. In contrast, acute acetazolamide produced no change in binding despite eliciting a dramatic diuresis. Chronic HCTZ (5 days) and chronic furosemide (7 days) increased binding of 3H-metolazone by 46% (P less than 0.001) and by 101% (P less than 0.001), respectively. Variation of dietary sodium intake over a range that allowed normal growth of the animal and that produced urinary excretion of Na varying from 0.28 to 2.62 mEq/100 g/day failed to alter the density of binding of 3H-metolazone. These studies are the first indication that the density of the thiazide receptor is regulated by a variety of both acute and chronic conditions that have previously been associated with changes in transport, ultrastructure or Na-K-ATPase activity in the distal nephron.(ABSTRACT TRUNCATED AT 250 WORDS)
Chen
Z F
ZF
Department of Medicine, University of California, San Diego, La Jolla 92093-0623.
Vaughn
D A
DA
Beaumont
K
K
Fanestil
D D
DD
D000086:Acetazolamide / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins; D004232:Diuretics / Q000494:pharmacology*; D005665:Furosemide / Q000494:pharmacology; D006852:Hydrochlorothiazide / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008788:Metolazone / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011955:Receptors, Drug / Q000187:drug effects / Q000378:metabolism; D049992:Sodium Chloride Symporters; D012982:Sodium, Dietary / Q000008:administration & dosage*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters
D002352:Carrier Proteins; D004232:Diuretics; D011955:Receptors, Drug; C578876:Slc12a3 protein, rat; D049992:Sodium Chloride Symporters; D012982:Sodium, Dietary; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters; C064415:thiazide receptor; D006852:Hydrochlorothiazide; D005665:Furosemide; D000254:Sodium-Potassium-Exchanging ATPase; D000086:Acetazolamide; D008788:Metolazone