ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Abstract: The effects of angiotensin II (AII) and related peptides on the mobilization of internal Ca2+ were studied in a subclone of NG108–15 cells. The subclone, C1, was prepared by fluorescence-activated cell cloning using a rapid response kinetics and a large response magnitude following stimulation by AII as the selection criteria. Angiotensin I, AII, and angiotensin III (AIII) stimulated Ca2+ mobilization in the C1 cells in a concentration-dependent manner (1 nM-100 μM), yielding EC50 values of 437 ± 80 nM (n = 4; slope = 1.6 ± 0.3), 57 ± 8 nM (n = 12; slope = 1.5 ± 0.3), and 36 ± 5 nM (n = 7; slope = 1.4 ± 0.3), respectively. AIII was significantly more potent than AII (p 〈 0.05). In contrast, Des-Phe8-AII, AII-hexapeptide (AII 3–8), and p-NH2-Phe6-AII (1–10 μM) were inactive as agonists. Although the effects of AII and AIII in C1 and parent NG108–15 cells were totally inhibited by the AT1 receptor-selective nonpeptide antagonist, DUP-753 (0.3–1 μM), the AT2-selective antagonists, EXP-655 and CGP42112A (1–10 μM), failed to block the effects of AII. DUP-753 (0.3–100 nM) produced dextral shifts of the AII-induced concentration-response curves and yielded an estimated affinity constant (pA2) of 8.5 ± 0.2 (n = 16) using single-point analysis involving different concentrations of DUP-753. These data compared well with those obtained for the inhibition of AII-induced aortic contractions by DUP-753 (pA2= 8.5) reported previously by others. These data strongly support the identification of an AT1-angiotensin receptor subtype in the NG108–15. C1 subclone that is coupled to a Ca2+ mobilization signal transduction mechanism.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1471-4159.1992.tb10065.x
Permalink
