BHQ is a selective inhibitor of endoplasmic reticulum Ca2+-ATPase.
Endoplasmic reticulum Ca2+-ATPase (SR Ca2+-ATPase) is a Ca2+-ATPase and transfers Ca2+ from the cytosol of the cell to the lumen of the sarcoplasmic reticulum (SR) during muscle relaxation.
BHQ is a selective SR Ca2+-ATPase inhibitor. In rat basophilic leukaemia cells, BHQ (10 μM) blocked inward rectifier potassium current and might cause depolarization of the cell and affect Ca2+ influx [1]. In aortic rings at rest or depolarised with 80 mM K+ in the presence of 1 mM nifedipine, BHQ induced a slow tonic contraction. At 20 mM K+, BHQ increased Ca2+-induced contraction. However, BHQ inhibited Ca2+-induced contraction at 40, 80 and 128 mM K+ [2]. In smooth muscle cells from the rat tail artery, BHQ reduced L-type Ca2+ current (ICa(L)) with IC50 value of 66.7 μM in a concentration- and voltage-dependent way. BHQ increased superoxide anion formation, which was markedly inhibited by superoxide dismutase (SOD). These results suggested that BHQ inhibited ICa(L) by the generation of superoxide anion [3]. In Madin Darby canine kidney (MDCK) cells, BHQ increased [Ca2+]i with EC50 value of 40 μM in a dose-dependent way, which was contributed by depleting the endoplasmic reticulum Ca2+ store followed by capacitative Ca2+ entry [4].
References:
[1]. Hasséssian H, Vaca L, Kunze DL. Blockade of the inward rectifier potassium current by the Ca(2+)-ATPase inhibitor 2',5'-di(tert-butyl)-1,4-benzohydroquinone (BHQ). Br J Pharmacol, 1994, 112(4): 1118-1122.
[2]. Fusi F, Gorelli B, Valoti M, et al. Effects of 2,5-di-t-butyl-1,4-benzohydroquinone (BHQ) on rat aorta smooth muscle. Eur J Pharmacol, 1998, 346(2-3): 237-243.
[3]. Fusi F, Saponara S, Gagov H, et al. 2,5-Di-t-butyl-1,4-benzohydroquinone (BHQ) inhibits vascular L-type Ca(2+) channel via superoxide anion generation. Br J Pharmacol, 2001, 133(7): 988-996.
[4]. Jan CR, Ho CM, Wu SN, et al. Mechanism of rise and decay of 2,5-di-tert-butylhydroquinone-induced Ca2+ signals in Madin Darby canine kidney cells. Eur J Pharmacol, 1999, 365(1): 111-117.
