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Comparative Study
.1999 Sep;128(1):13-20.
doi: 10.1038/sj.bjp.0702751.

Functional characterization of agonists at recombinant human 5-HT2A, 5-HT2B and 5-HT2C receptors in CHO-K1 cells

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Comparative Study

Functional characterization of agonists at recombinant human 5-HT2A, 5-HT2B and 5-HT2C receptors in CHO-K1 cells

R H Porter et al. Br J Pharmacol.1999 Sep.

Abstract

1. The goal of this study was to characterize the agonist pharmacology of human 5-HT2A, 5-HT2B and 5-HT2C (VSV) receptors expressed in CHO-K1 (Chinese hamster ovary) cells. 2. We used a fluorometric imaging plate reader (FLIPR) which allows rapid detection of rises in intracellular calcium levels upon the addition of agonists. 3. Stimulation of all three receptors by 5-HT caused a robust concentration dependent increase in intracellular calcium levels. No such effect was observed from non-transfected control CHO-K1 cells. 4. The rank order of potency of agonists at the different receptor subtypes varied. Tryptamines, BW-723C86, d-norfenfluramine, Ro 60-0175 and LSD exhibited the following rank order of potency; 5-HT2B>5-HT2C>5-HT2A. Piperazines such as m-Chlorophenylpiperazine (mCPP), ORG-12962, MK-212 and also ORG-37684 exhibited a rank order of potency of 5-HT2C>5-HT2B>5-HT2A. The phenylisopropylamines DOI and DOB had a rank order of 5-HT2A>5-HT2B>5-HT2C. 5. Many agonists tested had partial agonist actions when compared to 5-HT, and a wide range of relative efficacies were exhibited, which was cell line dependent. For example, mCPP had a relative efficacy of 65% at 5-HT2C receptors but <25% at either 5-HT2A or 5-HT2B receptors. 6. Interpretation of literature values of functional assays using different cell lines, different receptor expression levels and different receptor isoforms, is complex. Species differences and the previous use of antagonist radioligands to characterize agonist potency in binding assays emphasizes the importance of studying agonists in the same experiment using the same assay conditions and parental cell lines.

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Figures

Figure 1
Figure 1
Structures of the compounds studied. Abbreviations: 5-CT, 5-carboxamidotryptamine; α-Me-5-HT, α-methyl-5-hydroxytryptamine; 2-Me-5-HT, 2-methyl-5-HT; LSD, lysergic acid diethylamide; DOI, 2,5-dimethoxy-4-iodoamphetamine hydrobromide; DOB, 2,5-dimethoxy-4-bromoamphetamine hydrochloride.
Figure 2
Figure 2
Time course of calcium signal following compound addition on cells expressing (A) 5-HT2A receptors, (B) 5-HT2B receptors and (C) 5-HT2C receptors. Results are the fluorescence measurements taken from a single 96 well plate where 10 μM compound is added after 10 s. The data is from a single representative experiment that was repeated at least three times. Each data point depicting the average fluorescence value was performed in duplicate.
Figure 2
Figure 2
Time course of calcium signal following compound addition on cells expressing (A) 5-HT2A receptors, (B) 5-HT2B receptors and (C) 5-HT2C receptors. Results are the fluorescence measurements taken from a single 96 well plate where 10 μM compound is added after 10 s. The data is from a single representative experiment that was repeated at least three times. Each data point depicting the average fluorescence value was performed in duplicate.
Figure 2
Figure 2
Time course of calcium signal following compound addition on cells expressing (A) 5-HT2A receptors, (B) 5-HT2B receptors and (C) 5-HT2C receptors. Results are the fluorescence measurements taken from a single 96 well plate where 10 μM compound is added after 10 s. The data is from a single representative experiment that was repeated at least three times. Each data point depicting the average fluorescence value was performed in duplicate.
Figure 3
Figure 3
Concentration response curves at 5-HT2A, 5-HT2B and 5-HT2C receptors. Data points represent the maximum fluorescence signal obtained at each concentration and are representative from a single experiment performed in duplicate that was repeated 3–8 times.
Figure 3
Figure 3
Concentration response curves at 5-HT2A, 5-HT2B and 5-HT2C receptors. Data points represent the maximum fluorescence signal obtained at each concentration and are representative from a single experiment performed in duplicate that was repeated 3–8 times.
Figure 3
Figure 3
Concentration response curves at 5-HT2A, 5-HT2B and 5-HT2C receptors. Data points represent the maximum fluorescence signal obtained at each concentration and are representative from a single experiment performed in duplicate that was repeated 3–8 times.
Figure 3
Figure 3
Concentration response curves at 5-HT2A, 5-HT2B and 5-HT2C receptors. Data points represent the maximum fluorescence signal obtained at each concentration and are representative from a single experiment performed in duplicate that was repeated 3–8 times.
Figure 3
Figure 3
Concentration response curves at 5-HT2A, 5-HT2B and 5-HT2C receptors. Data points represent the maximum fluorescence signal obtained at each concentration and are representative from a single experiment performed in duplicate that was repeated 3–8 times.
Figure 3
Figure 3
Concentration response curves at 5-HT2A, 5-HT2B and 5-HT2C receptors. Data points represent the maximum fluorescence signal obtained at each concentration and are representative from a single experiment performed in duplicate that was repeated 3–8 times.
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