Inhibition of polycystin-L channel by the Chinese herb Sparganum stoloniferum Buch.-Ham.
The Chinese herb Sparganum stoloniferum Buch.-Ham. (SBH) is frequently used to improve blood circulation and to rehabilitate vascular obstruction in traditional Chinese medicine. It was recently reported that SBH reduces the proliferation of renal epithelial cells stimulated by epidermal growth factor (EGF), and inhibits the phosphorylation of the EGF receptor. SBH has also been used as a trial drug to treat polycystic kidney disease (PKD) patients in China. The potential molecular actions of SBH on PKD remain unknown. Autosomal dominant PKD (ADPKD) is associated with mutations in polycystin-1 or polycystin-2 (PC2). PC2 and its homologue, polycystin-L (PCL), are nonselective cation channels permeable to potassium, sodium, and calcium. Here, we examine the effects of SBH on the human PCL channel expressed in Xenopus oocytes, using 2-microelectrode voltage-clamp electrophysiology and radiotracer uptake measurements. In PCL-expressing oocytes, with or without preincubation with SBH, the PCL channel was inhibited by SBH in a dose-dependent and reversible manner; a concentration of 2% SBH completely abolished the channel activation. The IC50 value for SBH was 0.48% +/- 0.03%, with a 10-min preincubation period. SBH was also found to inhibit the PCL-mediated 45Ca tracer uptake in oocytes. Our study suggests that SBH contains 1 or more yet-to-be determined components that are inhibitors of PCL channel. The therapeutic potential of SBH for ADPKD and its chemical composition remain to be investigated.
Li
Fang
F
Membrane Protein Research Group, Department of Physiology, University of Alberta, 729 Medical Sciences Building, Edmonton, AB T6G 2H7, Canada.
Dai
Xiao-Qing
XQ
Li
Qiang
Q
Wu
Yuliang
Y
Chen
Xing-Zhen
XZ
D000818:Animals; D015220:Calcium Channels; D002478:Cells, Cultured; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D006801:Humans; D008562:Membrane Glycoproteins / Q000502:physiology*; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D010750:Phosphoproteins / Q000502:physiology*; D010936:Plant Extracts / Q000494:pharmacology; D011956:Receptors, Cell Surface; D013032:Sparganum / Q000737:chemistry*; D014981:Xenopus
D015220:Calcium Channels; D004365:Drugs, Chinese Herbal; D008562:Membrane Glycoproteins; C117185:PKD2L1 protein, human; D010750:Phosphoproteins; D010936:Plant Extracts; D011956:Receptors, Cell Surface