PMID- 11487507
OWN - NLM
STAT- MEDLINE
DCOM- 20011004
LR  - 20191210
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 133
IP  - 7
DP  - 2001 Aug
TI  - 2,5-Di-t-butyl-1,4-benzohydroquinone (BHQ) inhibits vascular L-type Ca(2+) 
      channel via superoxide anion generation.
PG  - 988-96
AB  - The aim of the present study was to investigate the effects of 
      2,5-di-t-butyl-1,4-benzohydroquinone (BHQ), an inhibitor of the sarco-endoplasmic 
      reticulum Ca(2+)-ATPase (SERCA), on the whole-cell voltage-dependent L-type 
      Ca(2+) current (I(Ca(L))) of freshly isolated smooth muscle cells from the rat 
      tail artery using the patch-clamp technique. BHQ, added to the perfusion 
      solution, reduced I(Ca(L)) in a concentration- (IC(50)=66.7 microM) and 
      voltage-dependent manner. This inhibition was only partially reversible. BHQ 
      shifted the voltage dependence of the steady-state inactivation curve to more 
      negative potentials by 7 mV in the mid-potential of the curve, without affecting 
      the activation curve as well as the time course of I(Ca(L)) inactivation. 
      Preincubation of the cells either with 10 microM cyclopiazonic acid, a SERCA 
      inhibitor, or with 3 mM diethyldithiocarbamate, an inhibitor of intracellular 
      superoxide dismutase (SOD), did not modify BHQ inhibition of I(Ca(L)). On the 
      contrary, this effect was no longer evident when SOD (250 u ml(-1)) was added to 
      the perfusion medium. Either in the presence or in the absence of cells, BHQ gave 
      rise to superoxide anion formation, which was markedly inhibited by the addition 
      of SOD. These results indicate that, at micromolar concentrations, BHQ inhibits 
      vascular I(Ca(L)) by giving rise to the formation of superoxide anion which in 
      turn impairs the channel function.
FAU - Fusi, F
AU  - Fusi F
AD  - Istituto di Scienze Farmacologiche, Universita degli Studi di Siena, via 
      Piccolomini 170, 53100 Siena, Italy. fusif@unisi.it
FAU - Saponara, S
AU  - Saponara S
FAU - Gagov, H
AU  - Gagov H
FAU - Sgaragli, G
AU  - Sgaragli G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Calcium Channels, L-Type)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Hydroquinones)
RN  - 0 (Indoles)
RN  - 11062-77-4 (Superoxides)
RN  - 26XK13B61B (2,5-di-tert-butylhydroquinone)
RN  - 99Z2744345 (Ditiocarb)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 7.2.2.10 (Calcium-Transporting ATPases)
RN  - X9TLY4580Z (cyclopiazonic acid)
SB  - IM
MH  - Animals
MH  - Calcium Channels, L-Type/*drug effects/physiology
MH  - Calcium-Transporting ATPases/antagonists & inhibitors
MH  - Ditiocarb/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Inhibitors/*pharmacology
MH  - Hydroquinones/*pharmacology
MH  - Indoles/pharmacology
MH  - Male
MH  - Membrane Potentials/drug effects
MH  - Muscle, Smooth, Vascular/cytology/*drug effects/physiology
MH  - Rats
MH  - Superoxide Dismutase/pharmacology
MH  - Superoxides/*metabolism
PMC - PMC1572887
EDAT- 2001/08/07 10:00
MHDA- 2001/10/05 10:01
PMCR- 2002/08/01
CRDT- 2001/08/07 10:00
PHST- 2001/08/07 10:00 [pubmed]
PHST- 2001/10/05 10:01 [medline]
PHST- 2001/08/07 10:00 [entrez]
PHST- 2002/08/01 00:00 [pmc-release]
AID - 0704183 [pii]
AID - 10.1038/sj.bjp.0704183 [doi]
PST - ppublish
SO  - Br J Pharmacol. 2001 Aug;133(7):988-96. doi: 10.1038/sj.bjp.0704183.