PT  - JOURNAL ARTICLE
AU  - Jack H Taylor
AU  - Nancy A Schulte
AU  - Jeffrey A French
AU  - Myron L Toews
TI  - Binding Characteristics of Two Oxytocin Variants and Vasopressin at Oxytocin Receptors from Four Primate Species with Different Social Behavior Patterns
AID  - 10.1124/jpet.118.250852
DP  - 2018 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - jpet.118.250852
4099  - http://jpet.aspetjournals.org/content/early/2018/08/01/jpet.118.250852.short
4100  - http://jpet.aspetjournals.org/content/early/2018/08/01/jpet.118.250852.full
AB  - A clade of New World monkeys (NWM) exhibits considerable diversity in both oxytocin ligand (OT) and receptor (OTR) structure. Most notable is the variant Pro8-OT, with proline instead of leucine at the eighth position (Pro8-OT), resulting in a rigid bend in the peptide backbone. A higher proportion of species that express Pro8-OT also engage in biparental care and social monogamy. When marmosets (genus Callithrix), a biparental and monogamous Pro8-OT NWM species, are administered the ancestral Leu8-OT, there is no change in social behavior compared to saline treatment. However, when Pro8-OT is administered, marmosets' socio-sexual and prosocial behaviors are altered. The studies here tested the hypothesis that OTR binding affinities and OT-induced intracellular Ca2+ potencies would favor the native oxytocin ligand in OTRs from four primate species, each representing a unique combination of ancestral lineage, breeding system, and native OT ligand: human (Leu8-OT, monogamous, apes), macaque (Leu8-OT, nonmonogamous, Old World monkey), marmoset (Pro8-OT, monogamous, NWM) and Titi monkey (Leu8-OT, monogamous, NWM). OTRs were expressed in CHO cells and tested for intact-cell binding affinities for Pro8-OT, Leu8-OT, and arginine vasopressin (AVP), as well as intracellular Ca2+ signaling after stimulation with Pro8-OT, Leu8-OT and AVP. Contrary to our hypothesis, Pro8-OT bound at modestly higher affinities and stimulated calcium signaling at modestly higher potencies compared to Leu8-OT in all four primate OTRs. Thus differences downstream from ligand-receptor binding event are more likely to explain the different behavioral responses to these two ligands.