Amylin, calcitonin gene-related peptide, and adrenomedullin: effects on thiazide receptor and calcium.
We previously reported that salmon calcitonin, but not rat calcitonin, increased renal thiazide receptor (TZR) density and decreased renal calcium [urinary calcium excretion (U(Caex))] in the rat. Since calcitonins, islet amyloid polypeptide (amylin), calcitonin-gene related peptide (CGRP), and adrenomedullin interact with a family of calcitonin-related receptors, we examined the effects of these peptides on 1) TZR density, as quantitated by binding of [3H]metolazone to renal membranes; 2) plasma ionic composition; and 3) urinary electrolyte excretion. Subcutaneous amylin both increased TZR density nearly twofold and decreased U(Caex), with maximal effects by 24 h. The decreased U(Caex) occurred with plasma amylin levels in the physiological range, whereas the increased TZR did not reach maximum even with plasma amylin >100 times above normal. Similar doses of adrenomedullin increased TZR density modestly but without effect on U(Caex), whereas CGRP did not alter TZR density and tended to increase U(Caex). We propose that U(Caex) and TZR density in the rat kidney are regulated by rat amylin but not by rat calcitonin.
Blakely
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Department of Medicine, School of Medicine, University of California San Diego, La Jolla 92093, USA.
Vaughn
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Fanestil
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D053607:Adrenomedullin; D000682:Amyloid / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001581:Benzothiadiazines; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D002118:Calcium / Q000652:urine*; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism*; D004232:Diuretics; D004573:Electrolytes / Q000097:blood / Q000652:urine; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006400:Hematocrit; D058228:Islet Amyloid Polypeptide; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000187:drug effects / Q000378:metabolism*; D012474:Salmon; D049993:Sodium Chloride Symporter Inhibitors / Q000493:pharmacokinetics; D049992:Sodium Chloride Symporters; D064486:Solute Carrier Family 12, Member 3; D013045:Species Specificity; D027981:Symporters
D000682:Amyloid; D000959:Antihypertensive Agents; D001581:Benzothiadiazines; D002352:Carrier Proteins; D004232:Diuretics; D004573:Electrolytes; D058228:Islet Amyloid Polypeptide; D010455:Peptides; 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; D053607:Adrenomedullin; D015740:Calcitonin Gene-Related Peptide; D002118:Calcium