Figure 4.

Inhibition of hU-II-induced contraction of cat isolated femoral artery and thoracic aortae by 1 μM GSK248451 (panels a and b; K_bs 1.3 and 191.9 nM, respectively; Table 3) and 10 μM SB-710411 (panels c and d; K_bs 0.9 μM and >10 μM, respectively; Table 3). Both peptidic ligands behaved as hU-II antagonists in the femoral artery (no evidence of intrinsic contractile activity was observed during 30 min antagonist preincubation prior to construction of the hU-II concentration-contraction response curve) but were >10- to 100-fold less potent in the thoracic aorta (significant antagonism was only evident with SB-710411 in isolated femoral arteries). 1 μM urantide exhibited agonist activity in both cat isolated arteries and, therefore, K_b was not determined (Tables 2 and 3 and Figure 6).