Premium
Ca 2+ Release from Inositol 1,4,5‐Trisphosphate‐Sensitive Ca 2+ Store by Antidepressant Drugs in Cultured Neurons of Rat Frontal Cortex
Author(s) -
Shimizu Masami,
Nishida Akira,
Hayakawa Hiroshi,
Yamawaki Shigeto
Publication year - 1993
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1993.tb03190.x
Subject(s) - inositol , antidepressant , chemistry , cortex (anatomy) , inositol trisphosphate , neuroscience , biophysics , pharmacology , receptor , biochemistry , biology , hippocampus
The ability of antidepressant drugs (ADs) to increase the concentration of intracellular Ca 2+ ([Ca 2+ ] i ) was examined in primary cultured neurons from rat frontal cortices using the Ca 2+ ‐sensitive fluorescent indicator fura‐2. Amitriptyline, imipramine, desipramine, and mianserin elicited transient increases in [Ca 2+ ] i in a concentration‐dependent manner (100 μ M to 1 m M ). These four AD‐induced [Ca 2+ ] i increases were not altered by the absence of external Ca 2+ or by the presence of La 3+ (30 μ M ), suggesting that these ADs provoked intracellular Ca 2+ mobilization rather than Ca 2+ influx. All four ADs increased inositol 1,4,5‐trisphosphate (IP 3 ) contents by 20–60% in the cultured cells. The potency of the IP 3 production by these ADs closely correlated with the AD‐induced [Ca 2+ ] i responses. Pretreatment with neomycin, an inhibitor of IP 3 generation, significantly inhibited amitriptyline‐ and imipramine‐induced [Ca 2+ ] i increases. In addition, by initially perfusing with bradykinin (10 μ M ) or acetylcholine (10 μ M ), which can stimulate the IP 3 generation and mobilize the intracellular Ca 2+ , the amitriptyline responses were decreased by 76% and 69%, respectively. The amitriptyline‐induced [Ca 2+ ] i increases were unaffected by treatment with pertussis toxin. We conclude that high concentrations of amitriptyline and three other ADs mobilize Ca 2+ from IP 3 ‐sensitive Ca 2+ stores and that the responses are pertussis toxin‐insensitive. However, it seems unlikely that the effects requiring high concentrations of ADs are related to the therapeutic action.