Effects of calcium-modulating hormones on thiazide receptor density.
Thiazide diuretic drugs act in the distal convoluted tubule (DCT) to inhibit a Na+Cl- cotransporter and enhance reabsorption of luminal calcium. The density of receptors for thiazides in the rat DCT is known to be increased by adrenocortical steroids, furosemide, and bendroflumethiazide, but decreased by ischemia. Because the DCT is a physiologic site of action by calcitonin and parathyroid hormone, this study examined the effects of these calcitropic hormones in thyroparathyroidectomized Sprague-Dawley rats on (1) the density of the rat thiazide receptor (TZR), as quantitated by binding of (3H)metolazone to renal membranes, and (2) urinary electrolyte excretion rate. Salmon calcitonin (sCT) (20 to 100 ng/h) (1) increased the density of the renal TZR twofold, an effect that is maximal by 6 h after sCT administration, and (2) decreased urinary calcium excretion rate. Adequate dietary calcium must be provided for the effects of sCT to be observed. Regression analysis demonstrated that renal TZR density correlated negatively with total urinary calcium excretion rate but not with plasma calcium ion concentration. In addition, neither rat calcitonin (rCT), at doses that cause hypocalcemia, nor parathyroid hormone, at doses that cause hypercalcemia, produce direct effects on TZR density in the DCT of the thyroparathyroidectomized rat. Our findings indicate that upregulation of TZR by sCT, which occurs independently of plasma calcium-ion concentration, is likely via a calcitonin-like receptor other than that for rat calcitonin itself.
Blakely
P
P
Department of Medicine, School of Medicine, University of California, San Diego, La Jolla 92093-0623, USA.
Vaughn
D A
DA
Fanestil
D D
DD
D000818:Animals; D001581:Benzothiadiazines; D002116:Calcitonin / Q000494:pharmacology*; D002118:Calcium / Q000652:urine*; D002136:Calcium, Dietary / Q000494:pharmacology; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D004232:Diuretics; D007686:Kidney Tubules, Distal / Q000378:metabolism; D008788:Metolazone / Q000378:metabolism; D016105:Parathyroidectomy; D051381:Rats; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000096:biosynthesis* / Q000235:genetics; D049993:Sodium Chloride Symporter Inhibitors / Q000494:pharmacology*; D049992:Sodium Chloride Symporters; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters; D019379:Teriparatide / Q000494:pharmacology*; D013965:Thyroidectomy; D013974:Thyroxine / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects*
D001581:Benzothiadiazines; D002136:Calcium, Dietary; D002352:Carrier Proteins; D004232:Diuretics; D011955:Receptors, Drug; C578876:Slc12a3 protein, rat; D049993:Sodium Chloride Symporter Inhibitors; D049992:Sodium Chloride Symporters; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters; C064415:thiazide receptor; D019379:Teriparatide; C028815:salmon calcitonin; D002116:Calcitonin; D013974:Thyroxine; D002118:Calcium; D008788:Metolazone