Binding characteristics of two oxytocin variants and vasopressin at oxytocin receptors from four primate species with different social behavior patterns

Jack H. Taylor, Nancy A. Schulte, Jeffrey A. French, Myron L. Toews

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

A clade of New World monkeys (NWMs) exhibits considerable diversity in both oxytocin (OT) ligand and oxytocin receptor (OTR) structure. Most notable is the variant Pro 8 -OT, with proline instead of leucine at the eighth position, resulting in a rigid bend in the peptide backbone. A higher proportion of species that express Pro 8 -OT also engage in biparental care and social monogamy. When marmosets (genus Callithrix), a biparental and monogamous Pro 8 -OT NWM species, are administered the ancestral Leu8-OT, there is no change in social behavior compared with saline treatment. However, when Pro 8 -OT is administered, marmosets' sociosexual and prosocial behaviors are altered. The studies here tested the hypothesis that OTR binding affinities and OT-induced intracellular Ca 2+ potencies would favor the native OT ligand in OTRs from four primate species, each representing a unique combination of ancestral lineage, breeding system, and native OT ligand: Humans (Leu8-OT, monogamous, apes), macaques (Leu8-OT, nonmonogamous, Old World monkey), marmosets (Pro 8 -OT, monogamous, NWM), and titi monkeys (Leu8-OT, monogamous, NWM). OTRs were expressed in immortalized Chinese hamster ovary cells and tested for intact-cell binding affinities for Pro 8 -OT, Leu8-OT, and arginine vasopressin (AVP), as well as intracellular Ca 2+ signaling after stimulation with Pro 8 -OT, Leu8-OT, and AVP. Contrary to our hypothesis, Pro 8 -OT bound at modestly higher affinities and stimulated calcium signaling at modestly higher potencies compared with Leu8-OT in all four primate OTRs. Thus, differences downstream from a ligand-receptor binding event are more likely to explain the different behavioral responses to these two ligands.

Original languageEnglish (US)
Pages (from-to)101-107
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume367
Issue number1
DOIs
StatePublished - Oct 2018

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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