Tight binding of the angiotensin AT(1) receptor antagonist

Biochemical Pharmacology
F L FierensaG Vauquelin

Abstract

Angiotensin II induces angiotensin AT(1) receptor internalization via Clathrin coated pits formation. We investigated whether insurmountable inhibition by the non-peptide antagonist 2-ethoxy-1-[(2'-(1H-tetrazol-5-yl) biphenyl-4-yl) methyl]-1H-benzimidazoline-7-carboxylic acid (candesartan) was related to receptor internalization. Mild acid treatment can discriminate between internalized and cell surface bound [(3)H]angiotensin II. In contrast, it provides no information about the subcellular localization of bound [(3)H]candesartan since this binding is acid resistant. The internalization of [(3)H]angiotensin II is rapidly inhibited in the presence of 0.4 M sucrose. Yet, no such rapid effect was noticed for [(3)H]candesartan. [(3)H]candesartan displays insurmountable/long lasting binding to the vast majority of both wild type and L(314) truncated rat angiotensin AT(1A) receptors with impaired receptor internalization. In agreement with previously published AT(1) angiotensin receptor visualization experiments, the present data suggest that non-peptide antagonist-angiotensin AT(1) receptor complexes remain at the cell surface. Insurmountable antagonism of candesartan is therefore independent from receptor internalization via clath...Continue Reading

References

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Citations

Dec 31, 2002·European Journal of Pharmacology·Catherina Caballero-GeorgeArnold Vlietinck
Mar 1, 2002·Brain Research. Molecular Brain Research·José Luis AlbasanzMairena Martín
Sep 2, 2004·Nature Reviews. Drug Discovery·David C Swinney
May 8, 2015·Journal of Drug Targeting·Robert HennigAchim Goepferich
May 18, 2012·Clinical Science·Rajesh KumarKenneth M Baker
Dec 12, 2001·Circulation Research·J L CookR N Re

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