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
-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.