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The crustacean cardioactive peptide (CCAP) is an important neuropeptide involved in the regulation of a variety of physiological processes in arthropods. Although this family of peptides has an ancestral origin, its function remains poorly understood among protostome species - apart from arthropods. We functionally characterized three G protein-coupled receptors (GPCRs) in the oyster Crassostrea gigas, phylogenetically related to ecdysozoan CCAP receptors (CCAPRs) and to chordate neuropeptide S receptors (NPSRs). Cragi-CCAPR1 and Cragi