Effects of N-n-butyl haloperidol iodide on L-type calcium channels and intracellular free calcium in rat ventricular myocytes.
The ability of N-n-butyl haloperidol iodide (F2) to cause vasodilation, and thereby produce a cardioprotective effect, has been well documented. The aim of this study was to investigate whether F2 might act as a Ca2+ antagonist. Myocytes were obtained from rat heart, and the whole-cell patch-clamp technique was used to record Ca2+ current. Laser scanning confocal microscopy was used to measure intracellular free calcium ([Ca2+]i). The results obtained from this study demonstrate that F2 reduced calcium current (ICa) in a concentration-dependent manner with an IC50 of 1.19 micromol/L, upshifted the current-voltage curve of ICa, shifted the inactivation kinetics of ICa leftward, and slowed down the recovery of ICa from inactivation. F2 decreased the fluorescent intensity of [Ca2+]i elevation induced by KCl with an IC50 of 1.61 micromol/L, and had no effects on the intracellular calcium release induced by caffeine and inositol-1,4,5-trisphosphate. These findings indicate that F2 may act as a calcium antagonist, which could account for its cardiovascular benefits.
Huang
Zhanqin
Z
Department of Pharmacology, Shantou University Medical College, Xinling Road 22, Shantou 515041, China.
Shi
Ganggang
G
Gao
Fenfei
F
Zhang
Yanmei
Y
Liu
Xingping
X
Christopher
Theodore A
TA
Lopez
Bernard
B
Ma
Xinliang
X
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002478:Cells, Cultured; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D006220:Haloperidol / Q000031:analogs & derivatives* / Q000494:pharmacology; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects
D020746:Calcium Channels, L-Type; D000697:Central Nervous System Stimulants; C482574:N-n-butyl haloperidol iodide; D002110:Caffeine; D015544:Inositol 1,4,5-Trisphosphate; D006220:Haloperidol; D002118:Calcium