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 language||English (US)|
|Number of pages||7|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|State||Published - Oct 2018|
ASJC Scopus subject areas
- Molecular Medicine