| Summary: | 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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