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Eur J Pharmacol. 2004 May 25;492(2-3):113-6.

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

Author information

1
Vascular Biology, Cardiovascular and Urogenital CEDD, GlaxoSmithKline, 709 Swedeland Road, King of Prussia, PA 19406, USA. david_j_behm@gsk.com

Abstract

SB-710411 (Cpa-c[d-Cys-Pal-d-Trp-Lys-Val-Cys]-Cpa-amide) inhibited [(125)I]urotensin-II rat and monkey UT receptor binding (pK(i)s 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 (pK(b) 6.54+/-0.05), this ligand functioned as an agonist at the monkey UT receptor (pEC(50) 6.56+/-0.35, E(max) 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 (pEC(50)s 5.03+/-0.18 to 5.71+/-0.21, E(max)s 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.

PMID:
15178353
DOI:
10.1016/j.ejphar.2004.03.059
[Indexed for MEDLINE]

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