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The Journal of Neuroscience, December 1, 1998, 18(23):9812-9821

The Lymnaea Cardioexcitatory Peptide (LyCEP) Receptor: A G-Protein-Coupled Receptor for a Novel Member of the RFamide Neuropeptide Family

Cornelis P. Tensen^{1, 2}, Kingsley J. A. Cox³, August B. Smit², Roel C. van der Schors², Wolfgang Meyerhof⁴, Dietmar Richter⁴, Rudi J. Planta¹, Petra M. Hermann², Jan van Minnen², Wijnand P. M. Geraerts², Jaco C. Knol¹, Julian F. Burke³, Erno Vreugdenhil¹, and Harm van Heerikhuizen¹

Departments of ¹ Biochemistry and Molecular Biology and ² Molecular Neurobiology, Research Institute Neurosciences, Vrije Universiteit, 1081 HV Amsterdam, The Netherlands, ³ Sussex Neuroscience Research Centre, School of Biological Sciences, University of Sussex, Falmer, Brighton BN1 9QG, United Kingdom, and ⁴ Institut für Zellbiochemie und Klinische Neurobiologie, Universitäts-Krankenhaus Eppendorf, 20246 Hamburg, Germany

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 oocytes expressing GRL106 activated a calcium-dependent chloride channel. Using this response as a bioassay, we purified the ligand for GRL106, Lymnaea cardioexcitatory peptide (LyCEP), an RFamide-type decapeptide (TPHWRPQGRF-NH₂) displaying significant similarity to the Achatina cardioexcitatory peptide (ACEP-1) as well as to the recently identified family of mammalian prolactin-releasing peptides. In the Lymnaea brain, the cells that produce egg-laying hormone are the predominant site of GRL106 gene expression and appear to be innervated by LyCEP-containing fibers. Indeed, LyCEP application transiently hyperpolarizes isolated egg-laying hormone cells. In the Lymnaea pericardium, LyCEP-containing fibers end blindly at the pericardial lumen, and the heart is stimulated by LyCEP in vitro. These data confirm that LyCEP is an RFamide ligand for GRL106.

Key words: neuropeptide receptor; mollusc; HPLC; Xenopus oocyte; RFamide; orphan receptor

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Copyright © 1998 Society for Neuroscience  0270-6474/98/18239812-10$05.00/0

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