Differential agonistic and antagonistic effects of the urotensin-II ligand SB-710411 at rodent and primate UT receptors

SB-710411 (Cpa-c[d-Cys-Pal-d-Trp-Lys-Val-Cys]-Cpa-amide) inhibited [125I]urotensin-II rat and monkey UT receptor binding (pKis 7.50±0.07 and 6.82±0.06). However, whereas SB-710411 antagonized urotensin-II-induced inositol phosphate formation at the rat UT receptor (pKb 6.54±0.05), this ligand functioned as an agonist at the monkey UT receptor (pEC50 6.56±0.35, Emax 5.27±0.65-fold over basal). Indeed, in contrast to the rat UT receptor (and rat isolated arteries), SB-710411 exhibited intrinsic activity in monkey arteries acting as an efficacious vasoconstrictor (pEC50s 5.03±0.18 to 5.71±0.21, Emaxs 101±4 to 218±58% KCl). These data demonstrate that caution must be taken when extrapolating the pharmacology of a specific ligand(s) between the rodent and primate UT receptors. [Copyright &y& Elsevier]