Binding affinities of oxytocin, vasopressin, and Manning Compound at oxytocin and V1a receptors in Syrian hamster brains

Taylor, J. H.; McCann, K. E.; Ross, A. P.; Albers, H. E.

doi:10.1101/2020.03.18.995894

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bioRxiv · 10.1101/2020.03.18.995894

Binding affinities of oxytocin, vasopressin, and Manning Compound at oxytocin and V1a receptors in Syrian hamster brains

Taylor, J. H.·McCann, K. E.·Ross, A. P.·Albers, H. E.

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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, but typically their pharmacological properties are determined in only a few species. Syrian hamsters (Mesocricetus auratus) have a long history of use as a behavioral and biomedical model for the study of oxytocin and vasopressin, and more recently, hamsters have been used to investigate behavioral consequences of OT-mediated activation of V1aRs. We sought to determine the binding affinities of OT, AVP, and the selective V1aR antagonist, Manning compound, in OTRs and V1aRs found in hamster brains. We performed saturation binding asays to determine the Kd values for the selective OTR and V1aR radioligands, [125I]OVTA and [125I]LVA in hamster brains. We then performed competition binding assays to determine Ki values for OT, AVP, and Manning compond 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 nM; AVP-V1ar Ki=4.70 nM), and had the lowest affinity for their non-canonical ligands (OT-V1aR=495.2nM; AVP-OTR Ki=36.1 nM). Manning compound had the highest affinity for the V1aR (MC-V1aR Ki=6.87 nM; MC-OTR Ki=213.8 nM), but Manning compound was not as selective for the V1aR as has been reported in rat receptor. When comparing these data to previously published work, we found that the promiscuity of the V1aR in hamsters with respect to oxytocin and vasopressin binding is more similar to the promiscuity of the human V1aR than the rat V1aR receptor. Moreover, the selectivity of oxytocin at hamster receptors is more similar to the selectivity of oxytocin at human receptors than the selectivity of oxytocin at rat receptors. These data highlight the importance of determining the pharmacological properties of behaviorally relevant compounds in diverse models species.

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Taylor, J. H., McCann, K. E., Ross, A. P., Albers, H. E.. 2020-03-18. Binding affinities of oxytocin, vasopressin, and Manning Compound at oxytocin and V1a receptors in Syrian hamster brains. https://doi.org/10.1101/2020.03.18.995894

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