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

• Published in: Journal of experimental pharmacology Vol. 10; p. 1
• Main Authors: Jamil, Khurram, Pappas, Stephen Chris, Devarakonda, Krishna R
• Format: Journal Article
• Language: English
• Published: Dove Medical Press Limited 01.01.2018
• Subjects: Adenylic acid; Cyclic adenylic acid; Pituitary hormones
• ISSN: 1179-1454; 1179-1454
• DOI: 10.2147/JEP.S146034

Terlipressin, a synthetic, systemic vasoconstrictor with selective activity at vasopressin-1 ([V.sub.1]) receptors, is a pro-drug for the endogenous/natural porcine hormone [[Lys.sub.8]]-vasopressin (LVP). We investigated binding and receptor-mediated cellular activities of terlipressin, LVP, and endogenous human hormone [[Arg.sub.8]]-vasopressin (AVP) at [V.sub.1] and vasopressin-2 ([V.sub.2]) receptors. Cell membrane homogenates of Chinese hamster ovary cells expressing human [V.sub.1] and [V.sub.2] 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 [[.sup.3]H]AVP counts, and the activity was measured by fluorometric detection of intracellular calcium mobilization ([V.sub.1]) and cyclic adenosine monophosphate ([V.sub.2]). Binding potency at [V.sub.1] and [V.sub.2] was AVP>LVP >>terlipressin. LVP and terlipressin had approximately sixfold higher affinity for [V.sub.1] than for [V.sub.2]. Cellular activity potency was also AVP>LVP>>terlipressin. Terlipressin was a partial agonist at [V.sub.1] and a full agonist at [V.sub.2]; LVP was a full agonist at both [V.sub.1] and [V.sub.2]. The in vivo response to terlipressin is likely due to the partial [V.sub.1] agonist activity of terlipressin and full [V.sub.1] agonist activity of its metabolite, LVP. These results provide supportive evidence for previous findings and further establish terlipressin pharmacology for vasopressin receptors. Keywords: hormones, in vitro techniques, pharmacology, hepatorenal syndrome