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The Corpuscles of Stannius, Calcium-Sensing Receptor, and Stanniocalcin: Responses to Calcimimetics and Physiological Challenges

Faculty of Life Sciences (M.P.G., R.J.B.), University of Manchester, Manchester M13 9PT, United Kingdom; Department of Animal Physiology (G.F.), Radboud University Nijmegen, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands; and Department of Physiology and Pharmacology (G.F.W.), Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada N6A 5C1

Address all correspondence and requests for reprints to: Richard J. Balment, Ph.D., D.Sc., 3.614 Stopford Building, Oxford Road, Manchester M13 9PT, United Kingdom. E-mail: richard.balment{at}manchester.ac.uk.

This study has examined whether the calcium-sensing receptor (CaSR) plays a role in control of stanniocalcin-1 (STC-1), the dominant calcium regulatory hormone of fish, comparable with that demonstrated for CaSR in the mediation of ionized calcium regulation of PTH secretion in mammals. In a previous study, we have cloned flounder STC-1 from the corpuscles of Stannius (CS). Here, we report the cloning and characterization of the CS CaSR, and the in vivo responses of this system to altered salinity, EGTA induced hypocalcemia, and calcimimetic administration. Quantitative PCR analysis demonstrated, for the first time, that the CS are major sites of CaSR expression in flounder. Immunoblot analysis of CS proteins with CaSR-specific antibodies revealed a broad band of approximately 215–300 kDa under nonreducing conditions, and bands of approximately 215–300 kDa and approximately 120–150 kDa under reducing conditions. There were no differences in CS CaSR mRNA expression or plasma STC-1 levels between seawater and freshwater (FW)-adapted fish, although CS STC-1 mRNA expression was lower in FW animals. Immunoblots showed that glycosylated monomeric forms of the CaSR migrated at a lower molecular mass in CS samples from FW animals. The ip administration of EGTA rapidly induced hypocalcemia, and a concomitant lowering of plasma STC-1. Calcimimetic administration (1 mg/kg R-568) rapidly increased plasma STC-1 levels, and reduced plasma concentrations of calcium, phosphate, and magnesium when compared with S-568-treated controls. Together, these findings support an evolutionary conserved role for the CaSR in the endocrine regulation of calcium before the appearance of parathyroid glands in tetrapods.