Characterization of Inhibitory Effectiveness in Hyperpolarization-Activated Cation Currents by a Group of <i>ent</i>-Kaurane-Type Diterpenoids from <i>Croton tonkinensis</i>
Croton is an extensive flowering plant genus in the spurge family, Euphorbiaceae. Three croton compounds with the common <i>ent</i>-kaurane skeleton have been purified from <i>Croton tonkinensis</i>. Methods: We examined any modifications of croton components (i.e., croton-01...
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MDPI AG
2020-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/4/1268 |
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| author | Ping-Chung Kuo Yen-Chin Liu Yi-Ching Lo Sheng-Nan Wu |
| author_facet | Ping-Chung Kuo Yen-Chin Liu Yi-Ching Lo Sheng-Nan Wu |
| author_sort | Ping-Chung Kuo |
| collection | DOAJ |
| description | Croton is an extensive flowering plant genus in the spurge family, Euphorbiaceae. Three croton compounds with the common <i>ent</i>-kaurane skeleton have been purified from <i>Croton tonkinensis</i>. Methods: We examined any modifications of croton components (i.e., croton-01 [<i>ent</i>-18-acetoxy-7α-hydroxykaur-16-en-15-one], croton-02 [<i>ent</i>-7α,14β-dihydroxykaur-16-en-15-one] and croton-03 [<i>ent</i>-1β-acetoxy-7α,14β-dihydroxykaur-16-en-15-one] on either hyperpolarization-activated cation current (<i>I</i><sub>h</sub>) or <i>erg</i>-mediated K<sup>+</sup> current identified in pituitary tumor (GH<sub>3</sub>) cells and in rat insulin-secreting (INS-1) cells via patch-clamp methods. Results: Addition of croton-01, croton-02, or croton-03 effectively and differentially depressed <i>I</i><sub>h</sub> amplitude. Croton-03 (3 μM) shifted the activation curve of <i>I</i><sub>h</sub> to a more negative potential by approximately 11 mV. The voltage-dependent hysteresis of <i>I</i><sub>h</sub> was also diminished by croton-03 administration. Croton-03-induced depression of <i>I</i><sub>h</sub> could not be attenuated by SQ-22536 (10 μM), an inhibitor of adenylate cyclase, but indeed reversed by oxaliplatin (10 μM). The <i>I</i><sub>h</sub> in INS-1 cells was also depressed effectively by croton-03. Conclusion: Our study highlights the evidence that these <i>ent</i>-kaurane diterpenoids might conceivably perturb these ionic currents through which they have high influence on the functional activities of endocrine or neuroendocrine cells. |
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| language | English |
| last_indexed | 2024-04-13T16:07:11Z |
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| spelling | doaj.art-cb7512537c6b40da9de38d8209b76a832022-12-22T02:40:21ZengMDPI AGInternational Journal of Molecular Sciences1422-00672020-02-01214126810.3390/ijms21041268ijms21041268Characterization of Inhibitory Effectiveness in Hyperpolarization-Activated Cation Currents by a Group of <i>ent</i>-Kaurane-Type Diterpenoids from <i>Croton tonkinensis</i>Ping-Chung Kuo0Yen-Chin Liu1Yi-Ching Lo2Sheng-Nan Wu3School of Pharmacy, National Cheng Kung University Medical College, Tainan 70101, TaiwanDepartment of Anesthesiology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, TaiwanDepartment of Pharmacology, Kaohsiung Medical University, Kaohsiung 80708, TaiwanDepartment of Physiology, National Cheng Kung University Medical College, Tainan 70101, TaiwanCroton is an extensive flowering plant genus in the spurge family, Euphorbiaceae. Three croton compounds with the common <i>ent</i>-kaurane skeleton have been purified from <i>Croton tonkinensis</i>. Methods: We examined any modifications of croton components (i.e., croton-01 [<i>ent</i>-18-acetoxy-7α-hydroxykaur-16-en-15-one], croton-02 [<i>ent</i>-7α,14β-dihydroxykaur-16-en-15-one] and croton-03 [<i>ent</i>-1β-acetoxy-7α,14β-dihydroxykaur-16-en-15-one] on either hyperpolarization-activated cation current (<i>I</i><sub>h</sub>) or <i>erg</i>-mediated K<sup>+</sup> current identified in pituitary tumor (GH<sub>3</sub>) cells and in rat insulin-secreting (INS-1) cells via patch-clamp methods. Results: Addition of croton-01, croton-02, or croton-03 effectively and differentially depressed <i>I</i><sub>h</sub> amplitude. Croton-03 (3 μM) shifted the activation curve of <i>I</i><sub>h</sub> to a more negative potential by approximately 11 mV. The voltage-dependent hysteresis of <i>I</i><sub>h</sub> was also diminished by croton-03 administration. Croton-03-induced depression of <i>I</i><sub>h</sub> could not be attenuated by SQ-22536 (10 μM), an inhibitor of adenylate cyclase, but indeed reversed by oxaliplatin (10 μM). The <i>I</i><sub>h</sub> in INS-1 cells was also depressed effectively by croton-03. Conclusion: Our study highlights the evidence that these <i>ent</i>-kaurane diterpenoids might conceivably perturb these ionic currents through which they have high influence on the functional activities of endocrine or neuroendocrine cells.https://www.mdpi.com/1422-0067/21/4/1268crotonpituitary cellpancreatic β-cellhyperpolarization-activated cation current<i>erg</i>-mediated k<sup>+</sup> currentmembrane potential |
| spellingShingle | Ping-Chung Kuo Yen-Chin Liu Yi-Ching Lo Sheng-Nan Wu Characterization of Inhibitory Effectiveness in Hyperpolarization-Activated Cation Currents by a Group of <i>ent</i>-Kaurane-Type Diterpenoids from <i>Croton tonkinensis</i> International Journal of Molecular Sciences croton pituitary cell pancreatic β-cell hyperpolarization-activated cation current <i>erg</i>-mediated k<sup>+</sup> current membrane potential |
| title | Characterization of Inhibitory Effectiveness in Hyperpolarization-Activated Cation Currents by a Group of <i>ent</i>-Kaurane-Type Diterpenoids from <i>Croton tonkinensis</i> |
| title_full | Characterization of Inhibitory Effectiveness in Hyperpolarization-Activated Cation Currents by a Group of <i>ent</i>-Kaurane-Type Diterpenoids from <i>Croton tonkinensis</i> |
| title_fullStr | Characterization of Inhibitory Effectiveness in Hyperpolarization-Activated Cation Currents by a Group of <i>ent</i>-Kaurane-Type Diterpenoids from <i>Croton tonkinensis</i> |
| title_full_unstemmed | Characterization of Inhibitory Effectiveness in Hyperpolarization-Activated Cation Currents by a Group of <i>ent</i>-Kaurane-Type Diterpenoids from <i>Croton tonkinensis</i> |
| title_short | Characterization of Inhibitory Effectiveness in Hyperpolarization-Activated Cation Currents by a Group of <i>ent</i>-Kaurane-Type Diterpenoids from <i>Croton tonkinensis</i> |
| title_sort | characterization of inhibitory effectiveness in hyperpolarization activated cation currents by a group of i ent i kaurane type diterpenoids from i croton tonkinensis i |
| topic | croton pituitary cell pancreatic β-cell hyperpolarization-activated cation current <i>erg</i>-mediated k<sup>+</sup> current membrane potential |
| url | https://www.mdpi.com/1422-0067/21/4/1268 |
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