Receptor Binding Affinities of Synthetic Cannabinoids Determined by Non-Isotopic Receptor Binding Assay
A major predictor of the efficacy of natural or synthetic cannabinoids is their binding affinity to the cannabinoid type I receptor (CB 1 ) in the central nervous system, as the main psychological effects of cannabinoids are achieved via binding to this receptor. Conventionally, receptor binding ass...
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| Published in | Toxicological research (Seoul) Vol. 35; no. 1; pp. 37 - 44 |
|---|---|
| Main Authors | , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Singapore
한국독성학회
01.01.2019
Springer Singapore Korean Society of Toxicology |
| Subjects | |
| Online Access | Get full text |
| ISSN | 1976-8257 2234-2753 |
| DOI | 10.5487/TR.2019.35.1.037 |
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| Abstract | A major predictor of the efficacy of natural or synthetic cannabinoids is their binding affinity to the cannabinoid type I receptor (CB
1
) in the central nervous system, as the main psychological effects of cannabinoids are achieved via binding to this receptor. Conventionally, receptor binding assays have been performed using isotopes, which are inconvenient owing to the effects of radioactivity. In the present study, the binding affinities of five cannabinoids for purified CB
1
were measured using a surface plasmon resonance (SPR) technique as a putative non-isotopic receptor binding assay. Results were compared with those of a radio-isotope-labeled receptor binding assay. The representative natural cannabinoid Δ
9
-tetrahydrocannabinol and four synthetic cannabinoids, JWH-015, JWH-210, RCS-4, and JWH-250, were assessed using both the SPR biosensor assay and the conventional isotopic receptor binding assay. The binding affinities of the test substances to CB
1
were determined to be (from highest to lowest) 9.52 × 10
−13
M (JWH-210), 6.54 × 10
−12
M (JWH-250), 1.56 × 10
−11
M (Δ
9
-tetrahydrocannabinol), 2.75 × 10
−11
M (RCS-4), and 6.80 ×10
−11
M (JWH-015) using the non-isotopic method. Using the conventional isotopic receptor binding assay, the same order of affinities was observed. In conclusion, our results support the use of kinetic analysis via SPR in place of the isotopic receptor binding assay. To replace the receptor binding affinity assay with SPR techniques in routine assays, further studies for method validation will be needed in the future. |
|---|---|
| AbstractList | A major predictor of the efficacy of natural or synthetic cannabinoids is their binding affinity to the cannabinoid type I receptor (CB1) in the central nervous system, as the main psychological effects of cannabinoids are achieved via binding to this receptor. Conventionally, receptor binding assays have been performed using isotopes, which are inconvenient owing to the effects of radioactivity. In the present study, the binding affinities of five cannabinoids for purified CB1 were measured using a surface plasmon resonance (SPR) technique as a putative non-isotopic receptor binding assay. Results were compared with those of a radio-isotope-labeled receptor binding assay.
The representative natural cannabinoid Δ9-tetrahydrocannabinol and four synthetic cannabinoids, JWH-015, JWH- 210, RCS-4, and JWH-250, were assessed using both the SPR biosensor assay and the conventional isotopic receptor binding assay. The binding affinities of the test substances to CB1 were determined to be (from highest to lowest) 9.52 × 10−13 M (JWH-210), 6.54 × 10−12 M (JWH-250), 1.56 × 10−11 M (Δ9-tetrahydrocannabinol), 2.75 × 10−11 M (RCS-4), and 6.80 ×10−11 M (JWH-015) using the non-isotopic method. Using the conventional isotopic receptor binding assay, the same order of affinities was observed. In conclusion, our results support the use of kinetic analysis via SPR in place of the isotopic receptor binding assay. To replace the receptor binding affinity assay with SPR techniques in routine assays, further studies for method validation will be needed in the future. KCI Citation Count: 0 A major predictor of the efficacy of natural or synthetic cannabinoids is their binding affinity to the cannabinoid type I receptor (CB 1 ) in the central nervous system, as the main psychological effects of cannabinoids are achieved via binding to this receptor. Conventionally, receptor binding assays have been performed using isotopes, which are inconvenient owing to the effects of radioactivity. In the present study, the binding affinities of five cannabinoids for purified CB 1 were measured using a surface plasmon resonance (SPR) technique as a putative non-isotopic receptor binding assay. Results were compared with those of a radio-isotope-labeled receptor binding assay. The representative natural cannabinoid Δ 9 -tetrahydrocannabinol and four synthetic cannabinoids, JWH-015, JWH-210, RCS-4, and JWH-250, were assessed using both the SPR biosensor assay and the conventional isotopic receptor binding assay. The binding affinities of the test substances to CB 1 were determined to be (from highest to lowest) 9.52 × 10 −13 M (JWH-210), 6.54 × 10 −12 M (JWH-250), 1.56 × 10 −11 M (Δ 9 -tetrahydrocannabinol), 2.75 × 10 −11 M (RCS-4), and 6.80 ×10 −11 M (JWH-015) using the non-isotopic method. Using the conventional isotopic receptor binding assay, the same order of affinities was observed. In conclusion, our results support the use of kinetic analysis via SPR in place of the isotopic receptor binding assay. To replace the receptor binding affinity assay with SPR techniques in routine assays, further studies for method validation will be needed in the future. A major predictor of the efficacy of natural or synthetic cannabinoids is their binding affinity to the cannabinoid type I receptor (CB ) in the central nervous system, as the main psychological effects of cannabinoids are achieved via binding to this receptor. Conventionally, receptor binding assays have been performed using isotopes, which are inconvenient owing to the effects of radioactivity. In the present study, the binding affinities of five cannabinoids for purified CB were measured using a surface plasmon resonance (SPR) technique as a putative non-isotopic receptor binding assay. Results were compared with those of a radio-isotope-labeled receptor binding assay. The representative natural cannabinoid Δ -tetrahydrocannabinol and four synthetic cannabinoids, JWH-015, JWH-210, RCS-4, and JWH-250, were assessed using both the SPR biosensor assay and the conventional isotopic receptor binding assay. The binding affinities of the test substances to CB were determined to be (from highest to lowest) 9.52 × 10 M (JWH-210), 6.54 × 10 M (JWH-250), 1.56 × 10 M (Δ -tetrahydrocannabinol), 2.75 × 10 M (RCS-4), and 6.80 ×10 M (JWH-015) using the non-isotopic method. Using the conventional isotopic receptor binding assay, the same order of affinities was observed. In conclusion, our results support the use of kinetic analysis via SPR in place of the isotopic receptor binding assay. To replace the receptor binding affinity assay with SPR techniques in routine assays, further studies for method validation will be needed in the future. A major predictor of the efficacy of natural or synthetic cannabinoids is their binding affinity to the cannabinoid type I receptor (CB1) in the central nervous system, as the main psychological effects of cannabinoids are achieved via binding to this receptor. Conventionally, receptor binding assays have been performed using isotopes, which are inconvenient owing to the effects of radioactivity. In the present study, the binding affinities of five cannabinoids for purified CB1 were measured using a surface plasmon resonance (SPR) technique as a putative non-isotopic receptor binding assay. Results were compared with those of a radio-isotope-labeled receptor binding assay. The representative natural cannabinoid Δ9-tetrahydrocannabinol and four synthetic cannabinoids, JWH-015, JWH-210, RCS-4, and JWH-250, were assessed using both the SPR biosensor assay and the conventional isotopic receptor binding assay. The binding affinities of the test substances to CB1 were determined to be (from highest to lowest) 9.52 × 10-13 M (JWH-210), 6.54 × 10-12 M (JWH-250), 1.56 × 10-11 M (Δ9-tetrahydrocannabinol), 2.75 × 10-11 M (RCS-4), and 6.80 ×10-11 M (JWH-015) using the non-isotopic method. Using the conventional isotopic receptor binding assay, the same order of affinities was observed. In conclusion, our results support the use of kinetic analysis via SPR in place of the isotopic receptor binding assay. To replace the receptor binding affinity assay with SPR techniques in routine assays, further studies for method validation will be needed in the future.A major predictor of the efficacy of natural or synthetic cannabinoids is their binding affinity to the cannabinoid type I receptor (CB1) in the central nervous system, as the main psychological effects of cannabinoids are achieved via binding to this receptor. Conventionally, receptor binding assays have been performed using isotopes, which are inconvenient owing to the effects of radioactivity. In the present study, the binding affinities of five cannabinoids for purified CB1 were measured using a surface plasmon resonance (SPR) technique as a putative non-isotopic receptor binding assay. Results were compared with those of a radio-isotope-labeled receptor binding assay. The representative natural cannabinoid Δ9-tetrahydrocannabinol and four synthetic cannabinoids, JWH-015, JWH-210, RCS-4, and JWH-250, were assessed using both the SPR biosensor assay and the conventional isotopic receptor binding assay. The binding affinities of the test substances to CB1 were determined to be (from highest to lowest) 9.52 × 10-13 M (JWH-210), 6.54 × 10-12 M (JWH-250), 1.56 × 10-11 M (Δ9-tetrahydrocannabinol), 2.75 × 10-11 M (RCS-4), and 6.80 ×10-11 M (JWH-015) using the non-isotopic method. Using the conventional isotopic receptor binding assay, the same order of affinities was observed. In conclusion, our results support the use of kinetic analysis via SPR in place of the isotopic receptor binding assay. To replace the receptor binding affinity assay with SPR techniques in routine assays, further studies for method validation will be needed in the future. |
| Author | Choon-Gon Jang Soo Kyung Suh Yun Jeong Song Hye Jin Cha Sung Jin Kim Jaesuk Yun Young-Hoon Kim Jisoon Shin Da Eun Lee |
| AuthorAffiliation | 4 Neuroimmunology Lab, College of Pharmacy, Wonkwang University, Iksan, Korea 1 Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Chungju, Korea 2 Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon, Korea 3 Cosmetics Policy Division, Ministry of Food and Drug Safety, Chungju, Korea |
| AuthorAffiliation_xml | – name: 4 Neuroimmunology Lab, College of Pharmacy, Wonkwang University, Iksan, Korea – name: 1 Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Chungju, Korea – name: 2 Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon, Korea – name: 3 Cosmetics Policy Division, Ministry of Food and Drug Safety, Chungju, Korea |
| Author_xml | – sequence: 1 givenname: Hye Jin surname: Cha fullname: Cha, Hye Jin email: chahj1@korea.kr organization: Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety – sequence: 2 givenname: Yun Jeong surname: Song fullname: Song, Yun Jeong organization: Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety – sequence: 3 givenname: Da Eun surname: Lee fullname: Lee, Da Eun organization: Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety – sequence: 4 givenname: Young-Hoon surname: Kim fullname: Kim, Young-Hoon organization: Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety – sequence: 5 givenname: Jisoon surname: Shin fullname: Shin, Jisoon organization: Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety – sequence: 6 givenname: Choon-Gon surname: Jang fullname: Jang, Choon-Gon organization: Department of Pharmacology, School of Pharmacy, Sungkyunkwan University – sequence: 7 givenname: Soo Kyung surname: Suh fullname: Suh, Soo Kyung organization: Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety – sequence: 8 givenname: Sung Jin surname: Kim fullname: Kim, Sung Jin organization: Cosmetics Policy Division, Ministry of Food and Drug Safety – sequence: 9 givenname: Jaesuk surname: Yun fullname: Yun, Jaesuk organization: Neuroimmunology Lab, College of Pharmacy, Wonkwang University |
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| Cites_doi | 10.1016/j.phrs.2016.11.021 10.3389/fphar.2016.00415 10.1016/S0958-1669(98)80038-4 10.1016/j.toxlet.2016.01.001 10.1016/j.lpm.2016.11.014 10.1111/jpm.12297 10.1073/pnas.1503395112 10.1007/978-1-60327-567-5_5 10.1124/jpet.115.225326 10.1016/j.tips.2016.12.003 10.3390/molecules19032842 10.1007/978-1-4939-2239-0_9 10.1007/s11920-016-0694-1 10.1016/j.bios.2007.07.001 10.1002/0471142301.ns0707s02 10.1124/mol.56.3.611 10.3747/co.23.3487 10.1016/j.ab.2015.12.019 10.4062/biomolther.2014.039 10.1111/j.1574-6976.2000.tb00532.x 10.1124/jpet.116.234948 10.1038/sj.bjp.0707399 10.15585/mmwr.mm6540a4 10.2174/1381612822666160919093450 10.1016/j.biopsych.2016.02.001 10.1002/jcph.827 10.1016/j.pep.2004.10.026 10.1080/08897077.2016.1219438 10.1101/pdb.prot073080 |
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| Keywords | SUP> Receptor binding assay Synthetic cannabinoids Surface plasmon resonance Δ< Human cannabinoid type I receptor (CB1) THC 9< Δ ) Human cannabinoid type I receptor (CB Δ9-THC |
| Language | English |
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| Snippet | A major predictor of the efficacy of natural or synthetic cannabinoids is their binding affinity to the cannabinoid type I receptor (CB
1
) in the central... A major predictor of the efficacy of natural or synthetic cannabinoids is their binding affinity to the cannabinoid type I receptor (CB ) in the central... A major predictor of the efficacy of natural or synthetic cannabinoids is their binding affinity to the cannabinoid type I receptor (CB1) in the central... |
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| Title | Receptor Binding Affinities of Synthetic Cannabinoids Determined by Non-Isotopic Receptor Binding Assay |
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