Binding Characteristics of Two Oxytocin Variants and Vasopressin at Oxytocin Receptors from Four Primate Species with Different Social Behavior Patterns.

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-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-OT also engage in biparental care and social monogamy. When marmosets (genus )， a biparental and monogamous Pro-OT NWM species， are administered the ancestral Leu-OT， there is no change in social behavior compared with saline treatment. However， when Pro-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 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 (Leu-OT， monogamous， apes)， macaques (Leu-OT， nonmonogamous， Old World monkey)， marmosets (Pro-OT， monogamous， NWM)， and titi monkeys (Leu-OT， monogamous， NWM). OTRs were expressed in immortalized Chinese hamster ovary cells and tested for intact-cell binding affinities for Pro-OT， Leu-OT， and arginine vasopressin (AVP)， as well as intracellular Ca signaling after stimulation with Pro-OT， Leu-OT， and AVP. Contrary to our hypothesis， Pro-OT bound at modestly higher affinities and stimulated calcium signaling at modestly higher potencies compared with Leu-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.