Modulation of calcitonin binding by calcium: differential effects of divalent cations.
Binding of salmon calcitonin to bovine hypothalamic membranes is enhanced about 25% by calcium with a half-maximal effect at 15 mM calcium. In contrast, membranes prepared from a cell line expressing a recombinant human calcitonin receptor show no effect of calcium under similar conditions. The hypothalamic calcitonin receptor solubilized with CHAPS detergent retains an apparent Kd of 0.3 nM for salmon calcitonin; however, binding of calcitonin to the detergent-solubilized receptor complex can be inhibited by divalent cations in order of potency Mn > Ca approximately Sr approximately Mg >> NaCl with Mn and Ca having apparent Ki's of 5 mM and 20 mM respectively. Dixon and Scatchard plots of Mn and Ca inhibition of binding to the soluble receptor complex suggest a noncompetitive mechanism of inhibition. Calcium also inhibits calcitonin binding to a detergent-solubilized recombinant human calcitonin receptor. Inhibition of calcitonin binding is observed using two independent methods for determining soluble receptor-hormone complex and inhibition is reversed by EDTA.
Stroop
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ZymoGenetics, Inc., Seattle, Washington 98105.
Moore
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Kuestner
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Thompson
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D000818:Animals; D002116:Calcitonin / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology*; D002417:Cattle; D004492:Edetic Acid / Q000494:pharmacology; D007031:Hypothalamus / Q000378:metabolism; D008345:Manganese / Q000494:pharmacology; D018003:Receptors, Calcitonin / Q000302:isolation & purification / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism
D018003:Receptors, Calcitonin; D011994:Recombinant Proteins; D008345:Manganese; D002116:Calcitonin; D004492:Edetic Acid; D002118:Calcium