Effects of chronic exposure to desipramine and mianserin on Ca2+ mobilization induced by noradrenaline, acetylcholine, and high K+ in rat frontocortical neurons.
We examined the chronic effects of desipramine and mianserin on increases of intracellular Ca2+ concentration ([Ca2+]i) induced by noradrenaline (NA), acetylcholine (ACh), or high K+ in cultured neurons of rat frontal cortex, using fluoromicroscopic analysis with Ca(2+)-sensitive dye fura-2. NA- and ACh-induced [Ca2+]i increases were abolished in the presence of 1 microM prazosin and 1 microM atropine, respectively, and partially inhibited in the absence of extracellular Ca2+. When cultures were treated with 1 microM desipramine for 5 days, the dose-dependent curves of NA- and ACh-induced (0.01-100 microM) [Ca2+]i increases were similar to those of the control cultures. Neither NA- nor ACh-induced [Ca2+]i increases were affected by desipramine exposure, even at a concentration of 10 microM. Treatment with mianserin (0.1, 1, or 10 microM) for 5 days had no effect on either NA- or ACh-induced [Ca2+]i increases. Additionally, [Ca2+]i increases induced by high K+ (12.5-50 mM) were not affected following chronic 10 microM desipramine exposure for 5 days. Thus, chronic antidepressant exposure does not modify the [Ca2+]i increased mediated by alpha 1-adrenoceptors, muscarinic cholinergic receptors, or voltage-sensitive Ca2+ channels. Changes in Ca2+ mobilization may not be one of the mechanisms of antidepressants.
Shimizu
M
M
Department of Psychiatry and Neuroscience, Kure National Hospital, Japan.
Nishida
A
A
Fukuda
H
H
Saito
H
H
Yamawaki
S
S
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003891:Desipramine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005625:Frontal Lobe / Q000187:drug effects*; D008803:Mianserin / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D051381:Rats
D008803:Mianserin; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium; D003891:Desipramine; D009638:Norepinephrine