Allatotropin (AT) related peptides L-ATRP and D2-ATRP diastereomers activate an endogenous receptor and suppress heart rate in the Pacific abalone Haliotis discus hannai

Allatotropin (AT) has been identified in many insects and plays important roles in the regulation of their intestinal contraction, heart rate, ion transport, and digestive enzyme secretion. However, information on AT-related bioinformatics in other animal phyla is scarce. In this study, we cloned a full-length cDNA encoding the AT-related peptide receptor (ATRPR) of the abalone Haliotis discus hannai (Hdh) and further characterized Hdh-ATRPR with its potential ligands, Hdh-ATRPs. In luciferase reporter and Ca²⁺ mobilization assays, Hdh-ATRPs, including a D-type Phe at the second amino acid position, Hdh-D2-ATRP, activated Hdh-ATRPR in a dose-dependent manner, whereas all-L-type Hdh-ATRP was a more potent ligand than Hdh-D2-ATRP. Furthermore, Hdh-ATRPs induced ERK1/2 phosphorylation in Hdh-ATRPR-expressing HEK293 cells, which was dose-dependently abolished by the PKC inhibitor Gö6983. The heart rate decreased significantly within 10 min when Hdh-D2-ATRP was injected into the adduct muscle sinus of abalone (0.2 or 1.0 µg/g body weight), while the abalone injected with a high concentration of Hdh-D2-ATRP (1.5 μg/g body weight) were sublethal within 5 h. Thus, Hdh-ATRP signaling is primarily linked to the Gαq/PKC and is possibly associated with heart rate regulation in abalone.