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• W2068654743 endingPage "1243" @default.
• W2068654743 startingPage "1235" @default.
• W2068654743 abstract "Adrenomedullin (ADM) and calcitonin gene-related peptide (CGRP) receptors and their respective ligands play important roles in cardiovascular (patho-)physiology. Functional expression of ADM and CGRP receptors requires the presence of the calcitonin receptor-like receptor (CRLR) together with receptor-activity-modifying proteins (RAMPs). We have characterized the expression patterns of CRLR and RAMP1 to RAMP3 in human cardiovascular-related tissues by quantitative polymerase chain reaction. We could identify high expression levels of CRLR, RAMP1, and RAMP2 in human heart and various blood vessels. RAMP3 expression in these tissues, however, was detectable at significantly lower levels. In addition, we describe here a novel, aequorin luminescence-based G protein-coupled receptor reporter assay that enables the real-time detection of receptor activation in living cells. In the assay system, intracellular cAMP levels are monitored with high sensitivity by using a modified, heteromultimeric cyclic nucleotide-gated channel mediating calcium influx. G_q-coupled receptor activation is detected via aequorin luminescence stimulated by calcium release from intracellular stores. Using this novel reporter assay, we established and characterized stable ADM1 and CGRP1 receptor cell lines. The peptide ligands ADM, CGRP1, and CGRP2 were characterized as potent agonists at their respective receptors. In contrast, intermedin acted as a weak agonist on both receptors and showed only partial agonism on the ADM1 receptor. Agonist activities were effectively antagonized by the receptor antagonists ADM(22-52) and CGRP(8-37). Various vasoactive ADM fragments were also characterized but showed no activity on the ADM1 receptor cell line. In addition, luminescence signal kinetics after activation of G_s- and G_q-coupled receptors were found to be markedly different." @default.
• W2068654743 created "2016-06-24" @default.
• W2068654743 creator A5033709539 @default.
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• W2068654743 date "2008-01-03" @default.
• W2068654743 modified "2023-09-30" @default.
• W2068654743 title "Pharmacological and Kinetic Characterization of Adrenomedullin 1 and Calcitonin Gene-Related Peptide 1 Receptor Reporter Cell Lines" @default.
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• W2068654743 doi "https://doi.org/10.1124/mol.107.042283" @default.
• W2068654743 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/18174292" @default.
• W2068654743 hasPublicationYear "2008" @default.
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