Binding affinities of oxytocin, vasopressin and Manning compound at oxytocin and V1a receptors in male Syrian hamster brains.

Abstract

Oxytocin (OT) and arginine vasopressin (AVP), as well as synthetic ligands targeting their receptors (OTR, V1aR), are used in a wide variety of research contexts, although their pharmacological properties are determined in only a few species. Syrian hamsters (Mesocricetus auratus) have a long history of use as a behavioural and biomedical model for the study of OT and AVP and, more recently, hamsters have been used to investigate behavioural consequences of OT-mediated activation of V1aR. We aimed to determine the binding affinities of OT, AVP and the selective V1aR antagonist, Manning compound, for OTR and V1aR in hamster brains. We performed saturation binding assays to determine the Kd values for the selective OTR and V1aR radioligands, [125 I]ornithine vasotocin analogue and [125 I]linear vasopressin antagonist. We then performed competition binding assays to determine Ki values for OT, AVP and Manning compound at both the OTR and V1aR. We found that OT and AVP each had the highest affinity for their canonical receptors (OT-OTR Ki=4.28 [95% confidence interval (CI)=2.9-6.3]nmolL-1 ; AVP-V1ar Ki=4.70 [95% CI=1.5-14.1]nmolL-1 ) and had the lowest affinity for their non-canonical ligands (OT-V1aR=495.2 [95% CI=198.5-1276]nmolL-1 ; AVP-OTR Ki=36.1 [95% CI=12.4-97.0]nmolL-1 ). Manning compound had the highest affinity for the V1aR (MC-V1aR Ki=6.87 [95% CI=4.0-11.9]nmolL-1 ; MC-OTR Ki=213.8 [95% CI=117.3-392.7]nmolL-1 ), although Manning compound was not as selective for the V1aR in hamsters as has been reported for the receptor in rats. When comparing these data with previously published work, we found that the promiscuity of the V1aR in hamsters with respect to OT and AVP binding is more similar to the promiscuity of the human V1aR than to the rat V1aR receptor. Moreover, the selectivity of OT at hamster receptors is more similar to the selectivity of OT at human receptors than the selectivity of OT at rat receptors. These data highlight the importance of determining the pharmacological properties of behaviourally relevant compounds in diverse model species.