Multiple amylin receptors arise from receptor activity-modifying protein interaction with the calcitonin receptor gene product
| Autor: | Nanda Tilakaratne, Steven M. Foord, George Christopoulos, Neil J. Fraser, Martin J. Main, Katie J. Perry, Yongyi Gao, Patrick M. Sexton, Maria Morfis |
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| Rok vydání: | 1999 |
| Předmět: |
medicine.medical_specialty
genetic structures Receptors Peptide Amylin CHO Cells Binding Competitive Receptor Activity-Modifying Proteins Internal medicine Cricetinae Chlorocebus aethiops medicine Cyclic AMP Animals Humans Calcitonin receptor Amylin binding Cells Cultured Pharmacology Receptor activity-modifying protein Dose-Response Relationship Drug Chemistry musculoskeletal neural and ocular physiology Intracellular Signaling Peptides and Proteins Membrane Proteins Receptor Activity-Modifying Protein 1 CALCRL Receptors Calcitonin Molecular biology Receptors Islet Amyloid Polypeptide Endocrinology RAMP2 RAMP1 COS Cells Molecular Medicine human activities |
| Zdroj: | Molecular pharmacology. 56(1) |
| ISSN: | 0026-895X |
| Popis: | Receptor activity-modifying proteins (RAMPs) are single-transmembrane proteins that transport the calcitonin receptor-like receptor (CRLR) to the cell surface. RAMP 1-transported CRLR is a calcitonin gene-related peptide (CGRP) receptor. RAMP 2- or RAMP 3-transported CRLR is an adrenomedullin receptor. The role of RAMPs beyond their interaction with CRLR, a class II G protein-coupled receptor, is unclear. In this study, we have examined the role of RAMPs in generating amylin receptor phenotypes from the calcitonin (CT) receptor gene product. Cotransfection of RAMP 1 or RAMP 3 with the human CT receptor lacking the 16-amino acid insert in intracellular domain 1 (hCTRI1-) into COS-7 cells induced specific 125I-labeled rat amylin binding. RAMP 2 or vector cotransfection did not cause significant increases in specific amylin binding. Competition-binding characterization of the RAMP-induced amylin receptors revealed two distinct phenotypes. The RAMP 1-derived amylin receptor demonstrated the highest affinity for salmon CT (IC50, 3.01 +/- 1.44 x 10(-10) M), a high to moderate affinity for rat amylin (IC50, 7.86 +/- 4.49 x 10(-9) M) and human CGRPalpha (IC50, 2.09 +/- 1.63 x 10(-8) M), and a low affinity for human CT (IC50, 4.47 +/- 0.78 x 10(-7) M). In contrast, whereas affinities for amylin and the CTs were similar for the RAMP 3-derived receptor, the efficacy of human CGRPalpha was markedly reduced (IC50, 1.12 +/- 0.45 x 10(-7) M; P |
| Databáze: | OpenAIRE |
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