Co-evolution of ligand-receptor pairs in the vasopressin/oxytocin superfamily of bioactive peptides

Publication Type:

Journal Article


J Biol Chem, Volume 271, Number 7, p.3619-3626 (1996)

DOI Name (links to online publication)



Amino Acid Sequence; analogs; &; derivatives; Animals; Base Sequence; Brain; Comparative Study; Dna; DNA Primers; drug effects; Evolution; Female; Ganglia; Invertebrate; genetics; Lymnaea; Male; mechanism; Membrane Proteins; metabolism; Molecular Sequenc


In order to understand the molecular mechanisms that underlie the co-evolution of related yet functionally distinct peptide-receptor pairs, we study receptors for the vasopressin-related peptide Lys-conopressin in the mollusc Lymnaea stagnalis. In addition to a previously cloned Lys-conopressin receptor (LSCPR1), we have now identified a novel Lys-conopressin receptor subtype, named LSCPR2. The two receptors have a differential distribution in the reproductive organs and the brain, which suggests that they are involved in the control of distinct aspects of reproduction and mediate transmitter-like and/or modulatory effects of Lys-conopressin on different types of central neurons. In contrast to LSCPR1, LSCPR2 is maximally activated by both Lys-conopressin and Ile-conopressin, an oxytocin-like synthetic analog of Lys-conopressin. Together with a study of the phylogenetic relationships of Lys-conopressin receptors and their vertebrate counterparts, these data suggest that LSCPR2 represents an ancestral receptor to the vasopressin/oxytocin receptor family in the vertebrates. Based on our findings, we provide a theory of the molecular co-evolution of the functionally distinct ligand-receptor pairs of the vasopressin/oxytocin superfamily of bioactive peptides