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 I) TZR density, as quantitated by binding of [H-3]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 calcitonin.