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 Leu(8)-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 (Leu(8)-OT, monogamous, apes), macaques (Leu(8)-OT, nonmonogamous, Old World monkey), marmosets (Pro(8)-OT, monogamous, NWM), and titi monkeys (Leu(8)-OT, monogamous, NWM). OTRs were expressed in immortalized Chinese hamster ovary cells and tested for intact-cell binding affinities for Pro(8)-OT, Leu(8)-OT, and arginine vasopressin (AVP), as well as intracellular Ca(2+) signaling after stimulation with Pro(8)-OT, Leu(8)-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 Leu(8)-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.