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Coexpression of Receptors for Adrenomedullin, Calcitonin Gene-Related Peptide, and Amylin in Pancreatic ß-Cells¹

Department of Cell and Cancer Biology, National Cancer Institute, National Institutes of Health (A.M., M.J.M., Y.W., F.C.), Bethesda, Maryland 20892; and Molecular Signaling Group, Clinical Sciences Research Center, St. Bartholomew’s and the Royal London School of Medicine and Dentistry (S.K.), London, United Kingdom E1 2AT

Address all correspondence and requests for reprints to: Dr. Alfredo Martínez, Department of Cell and Cancer Biology, National Cancer Institute, National Institutes of Health, Building 10, Room 13N262, 9000 Rockville Pike, Bethesda, Maryland 20892. E-mail: martineza{at}bprb.nci.nih.gov

Three receptors have been characterized by their ability to bind adrenomedullin (AM): L1, RDC1, and CRLR. Immunohistochemical analysis and RT-PCR showed that all three receptors are expressed by the insulin-producing cells of the islets of Langerhans. RDC1 and CRLR in the presence of particular modifying proteins can also bind calcitonin gene-related peptide (CGRP). Such data suggest that the inhibitory effect caused by both AM and CGRP on insulin secretion is mediated by a direct interaction with the ß-cell. We also identified receptors for amylin, the third member of the AM peptide family, in mouse insulin-secreting cells. The ß-cells located closer to the periphery of the islets had a stronger immunoreactivity for the AM/CGRP receptors. This observation could be related to a paracrine mechanism, given the proximity of AM- and CGRP-secreting cells (F and -cells, respectively), which are located at the periphery of the islets. Interestingly, the smooth muscle cells in the pancreatic vasculature expressed only RDC1, which is in agreement with physiological data showing that AM functions in the cardiovascular system are mainly mediated through a CGRP1 receptor. These data further implicate AM and the other components of its peptide family as important regulators of insulin release.

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