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Expression and Characterization of the Extracellular Ca²⁺-Sensing Receptor in Melanotrope Cells of Xenopus laevis

Department of Cellular Animal Physiology (M.J.J.V.D.H., D.T.W.M.O., W.J.J.M.S., V.L., H.G., E.W.R., B.G.J.), Institute of Cellular Signalling, Nijmegen Institute for Neurosciences, University of Nijmegen, 6525 ED Nijmegen, The Netherlands; and Endocrine-Hypertension Division (M.B.), Brigham and Women’s Hospital, Boston, Massachusetts 02115

Address all correspondence and requests for reprints to: M. J. J. van den Hurk, Department of Cellular Animal Physiology, University of Nijmegen, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands. E-mail: mavdhurk{at}sci.kun.nl.

The extracellular Ca²⁺-sensing receptor (CaR) is expressed in many different organs in various species, ranging from mammals to fish. In some of these organs, this G protein-coupled receptor is involved in the control of systemic Ca²⁺ homeostasis, whereas in other organs its role is unclear (e.g. in the pituitary gland). We have characterized the CaR in the neuroendocrine melanotrope cell of the intermediate pituitary lobe of the South African clawed toad Xenopus laevis. First, the presence of CaR mRNA was demonstrated by RT-PCR and in situ hybridization. Then it was shown that activation of the CaR by an elevated extracellular Ca²⁺ concentration and different CaR-activators, including L-phenylalanine and spermine, stimulates both Ca²⁺ oscillations and secretion from the melanotrope. Furthermore, it was revealed that activation of the receptor stimulates Ca²⁺ oscillations through opening of voltage-operated Ca²⁺ channels in the plasma membrane of the melanotropes. Finally, it was shown that the CaR activator L-phenylalanine could induce the biosynthesis of proopiomelanocortin in the intermediate lobe. Thus, in this study it is demonstrated that the CaR is present and functional in a defined cell type of the pituitary gland, the amphibian melanotrope cell.