Antibodies to Calcitonin Receptor Family (CTR, CRLR and RAMP1-3) - FocusOn 015

Introduction

The Calcitonin receptor plays an important role in the regulation of calcium and phosphate metabolism. It binds the peptide hormone Calcitonin, wich was named for its ability to reduce the blood calcium level.

Calcitonin (CT) is a 32 amino acid peptide cleaved from a larger prohormone. It contains a single disulfide bond, which causes the amino terminus to assume the shape of a ring. All members of the calcitonin family of peptides share this special secondary structure. Specific high-affinity receptors on the cell surface, mainly of osteoclasts mediate CT action. The first gene of the Calcitonin Receptor (CTR) has been cloned in 1991. CTR is a member of the seven-transmembrane, G protein-coupled receptor (GPCR) family. It is homologous to GPCRs in family "B" which typically recognizes regulatory peptides like secretin, glucagons etc. Interestingly, the specificity of CTR and CTR-like receptors (CRLRs) could be changed through receptor activity modifying proteins (also called Calcitonin-receptor-like receptor activity-modifying proteins or RAMPs). It is shown that Calcitonin Receptor-Like Receptor (CRLR) can function as either a CGRP receptor or an ADM receptor, depending upon which members of RAMP1-3 are expressed.

Interaction between CRLR and RAMP1 leads to receptors sensitive to CGRP, whereas the interaction with RAMP2 or 3 creates a receptor sensitive to adrenomedullin. The interaction between CTR and RAMP1 or RAMP3 gives however rise to an amylin sensitive receptor.

Antibody Tools for the Detection of CTR, CTR-like receptors and receptor activity modifying proteins

Acris Antibodies offers a panel of antibodies to the different members of the CTR family: CTR, CTLR, RAMP1, RAMP2 and RAMP3 can be detected by immunological methods like immunohistochemistry, Western blotting or ELISA.

Fig.1: Staining of human pulmonary artery for CLRL using rabbit polyclonal antibody code SP4082P

Fig.2: Staining of human arterial smooth muscle for CLRL using rabbit polyclonal antibody code SP4083P

Fig.3: Staining of human parathyroid gland for CTR using rabbit polyclonal antibody code SP4702P (Paraffin section)

Fig.4: Staining of human parathyroid gland for CTR using rabbit polyclonal antibody code SP4717P (Paraffin section)

Literature

Tolcos, M. et al. (2003). Ontogeny of calcitonin receptor mRNA and protein in the developing central nervous system of the rat. J. Comp. Neurol. 456: 29 – 38

Kovacs, C. S. et al. (2002). Calcitropic gene expression suggests a role for the intraplacental yolk sac in maternal-fetal calcium exchange. Am. J. Physiol. Endocrinol. Metab. 282: E721 – 732

Udawela M, Hay DL, Sexton PM. The receptor activity modifying protein family of G protein coupled receptor accessory proteins. Semin Cell Dev Biol. 2004 Jun;15(3):299-308.

Morfis M, Christopoulos A, Sexton PM. RAMPs: 5 years on, where to now? Trends Pharmacol Sci. 2003 Nov;24(11):596-601.

Purdue BW, Tilakaratne N, Sexton PM. Molecular pharmacology of the calcitonin receptor. Receptors Channels. 2002;8(3-4):243-55.

Fischer JA, Muff R, Born W. Functional relevance of G-protein-coupled-receptor-associated proteins, exemplified by receptor-activity-modifying proteins (RAMPs). Biochem Soc Trans. 2002 Aug; 30(4) : 455-60.

Pondel MD, Jagger C, Hebden C, Partington G, Mould R. Transcriptional regulation of the calcitonin receptor gene. Biochem Soc Trans. 2002 Aug;30(4):423-7.

Zaidi M, Inzerillo AM, Moonga BS, Bevis PJ, Huang CL Forty years of calcitonin--where are we now? A tribute to the work of Iain Macintyre, FRS. Bone. 2002 May;30(5):655-63.

Pondel M. Calcitonin and calcitonin receptors: bone and beyond. Int J Exp Pathol. 2000 Dec;81(6):405-22.

Born W, Fischer JA, Muff R Receptors for calcitonin gene-related peptide, adrenomedullin, and amylin: the contributions of novel receptor-activity-modifying proteins. Receptors Channels. 2002;8 (3-4):201-9.

Available antibody panel to the Calcitonin Receptor Family

CTR antibody (Calcitonin Receptor), CTLR (Calcitonin Receptor Like Receptor), RAMP1 (Calcitonin Receptor Like Receptor Activity Modifying Protein 1 antibody), RAMP2 (Calcitonin Receptor Like Receptor Activity Modifying Protein 2), RAMP3 (Calcitonin Receptor Like Receptor Activity Modifying Protein 3)