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The sequences of UCA, hUII and URP are shown in Supporting Information Table?S1, whereas the 2D structure of UCA is shown in Figure?1. Included in Supporting Information Table?S1 are chromatographic data describing the high level of purity of the analogs and their characterization by mass spectrometry. All peptides were tested in at least three separate experiments for their ability to bind to the hUII receptor stably transfected in CHO cells. Radioligand binding assay also showed that UCA is able to consistently and fully displace both radioligands, that is 125I-hUII and 125I-URP with an apparent IC50 value of 237?nM and 252?nM, respectively (Table?1). Ex vivo, hUII and URP evoked a dose-dependent contraction of rat aortic rings with a pEC50 of 8.89 �� 0.23 (Emax of 120 �� 8%; n = 10) and 8.12 �� 0.12 (Emax = 113 �� 5%; n = 10), respectively (Figure?2A). http://en.wikipedia.org/wiki/SWAP70 In opposition to hUII or URP, exposure to increasing concentrations of UCA, up to 10?��M, did not alter basal contractile tone (Figure?2A). Used as an antagonist, UCA suppressed http://www.selleckchem.com/products/BIBW2992.html concentration-dependently the maximum contractile response to hUII but not URP (Figure?2B and C; Table?2). For instance, pre-treatment with UCA at 10?8?M or 10?6?M produced a significant suppression of the maximum contractile response to hUII (Emax = 61% and 28%, respectively) with a non-significant shift in the concentration�Cresponse curve (Table?2). A further analysis of these results was performed based on a recent report of a non-peptidic UII insurmountable antagonist (Behm et?al., 2010). Consistent with non-competitive antagonism, the slope of the double reciprocal plot of agonist equiactive concentrations in the presence and absence of 10?nM UCA was linear with a slope of 2.36 �� 0.06, equating to a pKb of 8.13 (Figure?2D). Since no significant rightward shift or reduction http://www.selleckchem.com/products/BKM-120.html of efficacy associated with URP contractile response was observed following pre-treatment with UCA at either 10?8?M or 10?6?M (Figure?2B), this compound might be of pharmacologic/therapeutic value in order to discriminate hUII- and URP-associated signalling pathway and/or biological activity. Interspecies variability of several peptide and non-peptide ligands have complicated the interpretation of in vivo and in vitro studies. Therefore, functional experiments with non-rodent species, that is cynomolgus monkey, have been carried out with UCA. Consistent with the data generated in rat aorta, UCA significantly suppressed (P