In vitro effect of sanguinarine alkaloid on binding of [3H]candesartan to the human angiotensin AT1 receptor.

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Caballero-George C, Vanderheyden PM, Solis PN, Gupta MP, Pieters L, Vauquelin G, Vlietinck A

In vitro effect of sanguinarine alkaloid on binding of [3H]candesartan to the human angiotensin AT1 receptor.

Eur J Pharmacol. 2003 Jan 5;458(3):257-62.

PubMed ID

12504781 [ View in PubMed

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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]i midazole (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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Candesartan	Type-1 angiotensin II receptor	Protein	Humans	Yes	Antagonist	Details
Candesartan cilexetil	Type-1 angiotensin II receptor	Protein	Humans	Yes	Antagonist	Details