title: In vitro effect of sanguinarine alkaloid on binding of [3H]candesartan to the human angiotensin AT1 receptor.
abstract: The type of interaction of 5-methyl-2,3,7,8-bis(methylenedioxy)benzo[c]phenanthridinium (sanguinarine), an alkaloid isolated from the root of Bocconia frutescens L., with the human angiotensin AT(1) receptor was evaluated in both intact cells and membrane binding of [3H](2-ethoxy-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]-1H-benzimidazoline-7-carboxylic acid) ([3H]candesartan). The results indicate that the inhibition of [3H]candesartan binding by sanguinarine is independent of cell viability, since the alkaloid inhibited at a similar extent radioligand binding on both intact Chinese hamster ovary (CHO) cells transfected with the human angiotensin AT(1) receptor (hAT(1)) and their cell membranes (K(i)=0.14 and 1.10 microM, respectively). The unsuccessful recovery of [3H]candesartan binding after washing sanguinarine off the cells suggested a nearly irreversible or slow reversible interaction. Saturation binding studies showed a substantial reduction of the B(max) without affecting the K(d). In addition, the presence of 2-n-butyl-4chloro-5-hydroxymethyl-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole (losartan) could not prevent sanguinarine inhibition of [3H]candesartan binding neither. The present findings indicate that sanguinarine interacts with the receptor in a slow, nearly irreversible and noncompetitive manner.
authors.affiliation: Department of Pharmaceutical Sciences, University of Antwerp, Belgium.
authors.forename: Catherina
authors.initials: C
authors.lastname: Caballero-George
authors.forename: Patrick M L
authors.initials: PM
authors.lastname: Vanderheyden
authors.forename: Pablo N
authors.initials: PN
authors.lastname: Solis
authors.forename: Mahabir P
authors.initials: MP
authors.lastname: Gupta
authors.forename: Luc
authors.initials: L
authors.lastname: Pieters
authors.forename: Georges
authors.initials: G
authors.lastname: Vauquelin
authors.forename: Arnold
authors.initials: A
authors.lastname: Vlietinck
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000378:metabolism*; D053119:Benzophenanthridines; D001667:Binding, Competitive / Q000187:drug effects; D001713:Biphenyl Compounds; D016466:CHO Cells; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007546:Isoquinolines; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000235:genetics / Q000378:metabolism*; D013777:Tetrazoles / Q000378:metabolism*; D013936:Thymidine / Q000378:metabolism; D014162:Transfection; D014316:Tritium
chemical_list: D000470:Alkaloids; D001562:Benzimidazoles; D053119:Benzophenanthridines; D001713:Biphenyl Compounds; D007546:Isoquinolines; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D014316:Tritium; C005705:sanguinarine; C081643:candesartan; D013936:Thymidine