Effects of antidepressants on intracellular Ca2+ mobilization in CHO cells transfected with the human 5-HT2C receptors

• Published in: Biological psychiatry (1969) Vol. 39; no. 12; pp. 1000 - 1008
• Main Authors: AKIYOSHI, J, ISOGAWA, K, YAMADA, K, NAGAYAMA, H, FUJII, I
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Science 15.06.1996
• Subjects: Animals; Antidepressive Agents - pharmacology; Antidepressive Agents, Second-Generation - pharmacology; Biological and medical sciences; Calcium - metabolism; Calcium Channels - drug effects; Calcium Channels - genetics; CHO Cells; Cricetinae; Ergolines - pharmacokinetics; Humans; Intracellular Fluid - drug effects; Medical sciences; Mianserin - pharmacology; Neuropharmacology; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Radioligand Assay; Receptors, Serotonin - classification; Receptors, Serotonin - drug effects; Receptors, Serotonin - genetics; Serotonin Antagonists - pharmacology; Serotonin Receptor Agonists - pharmacology; Signal Transduction - drug effects; Signal Transduction - genetics; Transfection - genetics; Human; Signal transduction; Transfection; Calcium; Psychotropic; Antidepressant agent; Antagonist; Mechanism of action; In vitro; CHO cell line
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/0006-3223(95)00309-6

Serotonin 5-HT2C receptor-mediated intracellular Ca2+ mobilization was investigated in 5-HT2C receptors expressed in Chinese hamster ovary (CHO) cells; and fura-2/AM was used to investigate the regulation of 5-HT2C receptor function. CHO cells, transfected with a cDNA clone for the 5-HT2C receptor, expressed 287 fmol/mg of the receptor protein as determined by mianserin-sensitive [3H]-mesulergine binding (kd = 0.49 nM). The addition of 5-HT mobilized intracellular Ca2+ in a dose-dependent fashion, ranging from basal level of 99 +/- 1.8 nM up to 246 +/- 21.2 nM, with an EC50 value for 5-HT of .015 microM. Exposure to 5-HT, a 5-HT receptor agonist, mCPP [1-(3-chlorophenyl)piperazine dihydrochloride], a 5-HT2C agonist, and DOI [1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane], a 5-HT2C and 5-HT2 agonist, resulted in increased intracellular Ca2+ levels. Mianserin, mesulergine, ritanserin, and ketanserin each blocked 5-HT-mediated intracellular Ca2+ mobilization more effectively than spiperone. Mianserin and amoxapine inhibited 5-HT-mediated intracellular Ca2+ mobilization completely; amitriptyline, nortriptyline, and imipramine reduced it about 50%. These results suggest that antagonism in CHO cells transfected with human 5-HT2C receptors is a component of the serotonergic properties of a number of established antidepressants.