THE LYMNAEA CARDIOEXCITATORY PEPTIDE (LYCEP) RECEPTOR - A G-PROTEIN-COUPLED RECEPTOR FOR A NOVEL MEMBER OF THE RFAMIDE NEUROPEPTIDE FAMILY

A novel G-protein-coupled receptor (GRL106) resembling neuropeptide Y and tachykinin receptors was cloned from the mollusc Lymnaea stagnalis . Application of a peptide extract from the Lymnaea brain to Xenopus o ocytes expressing GRL106 activated a calcium-dependent chloride channe l. Using this response as a bioassay, we purified the ligand for GRL10 6, Lymnaea cardioexcitatory peptide (LyCEP), an RFamide-type decapepti de (TPHWRPQGRF-NH2) displaying significant similarity to the Achatina cardioexcitatory peptide (ACEP-1) as well as to the recently identifie d family of mammalian prolactin-releasing peptides. In the Lymnaea bra in, the cells that produce egg-laying hormone are the predominant site of GRL106 gene expression and appear to be innervated by LyCEP-contai ning fibers. Indeed, LyCEP application transiently hyperpolarizes isol ated egg-laying hormone cells. In the Lymnaea pericardium, LyCEP-conta ining fibers end blindly at the pericardial lumen, and the heart is st imulated by LyCEP in vitro. These data confirm that LyCEP is an RFamid e ligand for GRL106.