Isosteviol as a potassium channel opener to lower intracellular calcium concentrations in cultured aortic smooth muscle cells.
Isosteviol is a derivative of stevioside, a constituent of Stevia rebaudiana, and is commonly used as a non-caloric sugar substitute in Japan and Brazil. The present study attempted to elucidate the role of potassium (K (+)) channels in the action of isosteviol on intracellular calcium concentrations ([Ca (2+)]i) in cultured vascular smooth muscle (A7r5) cells using the Ca (2+)-sensitive dye Fura-2 as an indicator. The increase of [Ca (2+)]i in A7r5 cells produced by vasopressin (1 micromol/L) or phenylephrine (1 micromol/L) was attenuated by isosteviol from 0.01 micromol/L to 10 micromol/L. The attenuation by isosteviol of the vasopressin- and phenylephrine-induced increase in [Ca (2+)]i was inhibited by glibenclamide, apamin and 4-aminopyridine but not by charybdotoxin. Furthermore, the inhibitory action of isosteviol on [Ca (2+)]i was blocked when A7r5 cells co-treated with glibenclamide and apamin in conjunction with 4-aminopyridine were present. Therefore, not only did the ATP-sensitive potassium (K (ATP)) channel affect the action of isosteviol on [Ca (2+)]i modulation in A7r5 cells, but also those on the small conductance calcium-activated potassium (SK (Ca)) channels and voltage-gated (Kv) channels. However, the blockers of large-conductance Ca (2+)-activated potassium channels failed to modify the inhibitory action of isosteviol on [Ca (2+)]i. The obtained results indicated that a decrease of [Ca (2+)]i in A7r5 cells by isosteviol is mainly mediated by the selective opening of K (ATP) channel or/and SK (Ca) channel. Alteration in the Kv channel also plays a critical role in the inhibitory action of isosteviol.
Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan, R.O.C.
Kar-Lok
KL
Wong
Hung-Yu
HY
Yang
Paul
P
Chan
Tz-Hurng
TH
Cheng
Ju-Chi
JC
Liu
Feng-Lin
FL
Hsu
I-Min
IM
Liu
Yu-Wan
YW
Cheng
Juei-Tang
JT
Cheng
D000818:Animals; D001011:Aorta / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D004224:Diterpenes / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D045786:Diterpenes, Kaurane; D004305:Dose-Response Relationship, Drug; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D036625:Stevia
D004224:Diterpenes; D045786:Diterpenes, Kaurane; D010936:Plant Extracts; D024681:Potassium Channels, Calcium-Activated; C012042:steviol; D002118:Calcium