This paper is only available as a PDF. To read, Please Download here.
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 μM. 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.
Key Words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Biological PsychiatryAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Paradoxical increase of 5-hydroxytryptamine2 receptor and 5-hydroxytryptamine2 receptor mRNA in cerebellar granule cells after persistent 5-hydroxytryptamine2 receptors stimulation.Mol Pharmacol. 1993; 42: 349-355
- 5-hydroxytryptamine1C receptor density and mRNA levels in choroid plexus epithelial cells after treatment with mianserin and (−)-1-(4-bromo-2,5-dimethoxyphenyl)-2-aminopropane.Mol Pharmacol. 1993; 44: 725-730
- Behavioral evidence for functional interactions between 5-HT receptor subtypes in rats and mice.Br J Pharmacol. 1990; 101: 667-673
- Characterization of functional response in A9 cells transfected with cloned rat 5-HT1C receptors.Naunyn-Schmiedeberg's Arch Pharmacol. 1993; 347: 119-124
- Trazodone: A review of its pharmacological properties and therapeutic use in depression and anxiety.Drugs. 1981; 21: 401-429
- Chronic electroconvulsive seizures increase the expression of serotonin2 receptor mRNA in rat frontal cortex.J Neurochem. 1993; 61: 1270-1276
- Neuroendocrine regulation in depression: II. Discrimination of depressed from non-depressed patients.Arch Gen Psychiatry. 1976; 138: 1218-1221
- High-efficiency transformation of mammalian cells by plasmid DNA.Mol Cell Biol. 1987; 7: 2745-2752
- Relative efficacies of piperazine at the phosphoinositide hydrolysis-linked serotonergic (5-HT-2 and 5-HT-1c) receptors.J Pharmacol Exp Ther. 1987; 242: 552-557
- A unique serotonin receptor in choroid plexus is linked to phosphatidylinositol turnover.in: Proc Natl Acad Sci USA. 83. 1986: 4086-4088
- Evidence that phospholipid turnover is the signal transducing system coupled to serotonin-S2 receptor sites.J Biol Chem. 1985; 260: 7603-7608
- Regulation of receptor expression by agonists: Transcriptional and post-transcriptional control.Trends Neurosci. 1991; 14: 242-247
- Effects of antidepressant drugs on different receptors in the brain.Eur J Pharmacol. 1981; 70: 393-397
- Modulation of serotonin and corticosteroid gene expression in the rat hippocampus with circadian rhythm and stress.Mol Brain Res. 1995; 28: 186-192
- Molecular pharmacology and biology of 5-HT1C receptors.Trends Pharmacol Sci. 1988; 9: 89-94
- Evidence for a role of 5-HT1C receptors in the antiserotonergic properties of some antidepressant drugs.Eur J Pharmacol. 1993; 231: 223-229
- Molecular characterization of a functional cDNA encoding the serotonin 1c receptor.Science. 1988; 241: 558-564
- cDNA cloning of a serotonin 5-HT1C receptor by electrophysiological assays of mRNA-injected Xenopus oocytes.in: Proc Natl Acad Sci USA. 84. 1987: 4332-4336
- Serotonergic mechanisms of antidepressant drugs.Pharmacopsychiatry. 1981; 14: 35-40
- Mouse 5-hydroxytryptamine5A and 5-hydroxytryptamine5B receptors define a new family of serotonin receptors: Cloning, functional expression and chromosomal localization.Mol Pharmacol. 1993; 43: 313-319
- 5-HT1C receptor is a prominent serotonin receptor subtype in the central nervous system.in: Proc Natl Acad Sci USA. 86. 1989: 6793-6797
- Cloning and expression of a novel serotonin receptor with high affinity for tricyclic psychotropic drugs.Mol Pharmacol. 1993; 43: 320-327
- The binding of serotonergic ligands to the porcine choroid plexus: Characterization of a new type of serotonin recognition site.Eur J Pharmacol. 1985; 106: 539-546
- 5-hydroxytryptamine receptors.J Neurochem. 1993; 60: 408-416
- Distribution of the serotonin 5-HT2 receptor family mRNAs: Comparison between 5-HT2A and 5-HT2C receptor.Mol Brain Res. 1994; 23: 163-178
- Chronic mianserin treatment decreases 5-HT2 receptor binding without altering 5-HT2 receptor mRNA levels.Eur J Pharmacol. 1991; 207: 169-172
- Cloning of the human serotonin 5-HT2 and 5-HT1C receptor subtypes.Biochem Biophys Res Commun. 1991; 181: 1469-1478
- Serotonin1C receptor reserve in choroid plexus masks receptor subsensitivity.J Pharmacol Exp Ther. 1990; 252: 984-988
- Molecular cloning and expression of a 5-hydroxytryptamine7 serotonin receptor subtype.J Biol Chem. 1993; 268: 18200-18204
- Eating disorder and epilepsy in mice lacking 5-HT2C serotonin receptors.Nature. 1995; 374: 542-546
- Effects of antidepressants on serotonin-evoked current in Xenopus oocyte injected with rat brain m-RNA.Eur J Pharmacol. 1989; 186: 57-63
- 125I-Lysergic acid diethyamide binds to a novel serotonergic site on rat choroid plexus epithelial cells.J Neurosci. 1985; 5: 3178-3183
- 5HT2 receptors changes in major depression.Biol Psychiatry. 1990; 27: 489-496
Article info
Publication history
Received in revised form:
May 31,
1995
Received:
December 5,
1994
Identification
Copyright
© 1996 Society of Biological Psychiatry. Published by Elsevier Inc.
