In vitro binding and receptor-mediated activity of terlipressin at vasopressin receptors V 1 and V 2 .

Terlipressin, a synthetic, systemic vasoconstrictor with selective activity at vasopressin-1 (V) receptors, is a pro-drug for the endogenous/natural porcine hormone [Lys]-vasopressin (LVP). We investigated binding and receptor-mediated cellular activities of terlipressin, LVP, and endogenous human hormone [Arg]-vasopressin (AVP) at V and vasopressin-2 (V) receptors. Cell membrane homogenates of Chinese hamster ovary cells expressing human V and V receptors were used in competitive binding assays to measure receptor-binding activity. These cells were used in functional assays to measure receptor-mediated cellular activity of terlipressin, LVP, and AVP. Binding was measured by [H]AVP counts, and the activity was measured by fluorometric detection of intracellular calcium mobilization (V) and cyclic adenosine monophosphate (V). Binding potency at V and V was AVP>LVP>>terlipressin. LVP and terlipressin had approximately sixfold higher affinity for V than for V. Cellular activity potency was also AVP>LVP>>terlipressin. Terlipressin was a partial agonist at V and a full agonist at V; LVP was a full agonist at both V and V. The in vivo response to terlipressin is likely due to the partial V agonist activity of terlipressin and full V agonist activity of its metabolite, LVP. These results provide supportive evidence for previous findings and further establish terlipressin pharmacology for vasopressin receptors.