CHRONIC IMIPRAMINE ADMINISTRATION AMPLIFIES THE SEROTONIN(2A) RECEPTOR-INDUCED INTRACELLULAR CA2-CELLS THROUGH A CALMODULIN-DEPENDENT PATHWAY( MOBILIZATION IN C6 GLIOMA)
S. Muraoka et al., CHRONIC IMIPRAMINE ADMINISTRATION AMPLIFIES THE SEROTONIN(2A) RECEPTOR-INDUCED INTRACELLULAR CA2-CELLS THROUGH A CALMODULIN-DEPENDENT PATHWAY( MOBILIZATION IN C6 GLIOMA), Journal of neurochemistry, 71(4), 1998, pp. 1709-1718
In the present study, we examined whether chronic exposure of C6BU-1 c
ells to 100 nM of several different types of antidepressants directly
influences serotonin(2A) (5-HT2A) receptor-stimulated intracellular Ca
2+ mobilization, Imipramine, desipramine, clomipramine, and maprotilin
e amplified the 5-HT response at 18, but not at 2, h, Imipramine incre
ased the maximum response to 5-HT without altering the EC50 of the dos
e-response curve, This effect was time dependent and cycloheximide blo
cked the maximal induction, suggesting an essential role for protein s
ynthesis in this process. Previous exposure of the cells to thrombin o
r isoproterenol did not influence 5-HT2A receptor function and pretrea
tment with imipramine did not alter the thrombin- or bradykinin-induce
d Ca2+ mobilization, which indicates that the effects of imipramine ap
pear to be specific to the 5-HT2A receptor. The effect of imipramine w
as potently suppressed by a calmodulin antagonist, W-13, in a dose-dep
endent manner. Furthermore, this amplified 5-HT response was blocked b
y KN-93, but not by H-7, Taken together, these results suggest that im
ipramine has a modulatory effect on the 5-HT2A receptor-coupled intrac
ellular Ca2+ in C6 cells through a calmodulin-dependent pathway, possi
bly involving Ca2+/calmodulin kinase activation.