Effects of clomipramine and verapamil on 5-HT-induced intracellular calcium changes in individual C6 rat glioma cells.
The effects of antidepressants and calcium (Ca2+) antagonists on serotonin (5-HT)-induced Ca2+ increase were investigated in single C6BU-1 glioma cells with digital imaging microscopy. Application of 5-HT (100 nM-100 microM) caused a rapid and reversible rise of intracellular Ca2+ concentration ([Ca2+]i) in a concentration-dependent manner. In the absence of extracellular Ca2+, the sustained phase of the [Ca2+]i response was strongly reduced, which was greater than the suppression of the initial peak. This suggests that the peak value is mainly due to internal Ca2+ storage sites, and the sustained phase is mainly composed of Ca2+ influx. The sustained phase was significantly attenuated by 100 nM clomipramine and verapamil. The present findings demonstrate that clomipramine and verapamil, in their therapeutic concentrations, have a common action of inhibiting Ca2+ influx, and suggest that the calcium antagonistic effect may play an important role in clinical effects of antidepressants.
Yamaji
T
T
Department of Psychiatry and Neurosciences, Hiroshima University School of Medicine, Japan.
Kagaya
A
A
Okamoto
Y
Y
Hayashi
T
T
Motohashi
N
N
Yamawaki
S
S
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002997:Clomipramine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005910:Glioma / Q000188:drug therapy*; D051381:Rats; D012701:Serotonin / Q000494:pharmacology*; D013997:Time Factors; D014700:Verapamil / Q000494:pharmacology*
D012701:Serotonin; D014700:Verapamil; D002997:Clomipramine; D002118:Calcium