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Adrenomedullin (ADM) is a hypotensive peptide that belongs to a peptide superfamily, which includes the calcitonin gene-related peptide (CGRP) and amylin. ADM was originally identified in the adrenal medulla, where it is highly expressed. It is also produced by most contractile cells and is upregulated during sepsis and ischemia. Three distinct receptors have the ability to bind ADM and are designated ADM receptor (also designated L1), RDC-1 and the Calcitonin Receptor-Like Receptor (CRLR). The CRLR associates with receptor activity-modifying proteins (RAMPs), which determine the specificity of CRLR binding. Co-expression with RAMP1 results in CRLR binding to CGRP, whereas association with RAMP2 or 3 results in ADM binding. The ADM receptor, a seven transmembrane G protein-coupled receptor, specifically binds ADM and is highly expressed in heart, brain, skeletal muscle, the immune system, adrenal gland and liver. The ADM receptor mediates the signals produced by ADM through G proteins, which activate adenylate cyclase.
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