Phytoestrogen cimicifugoside-mediated inhibition of catecholamine secretion by blocking nicotinic acetylcholine receptor in bovine adrenal chromaffin cells.
We investigated the effect of the phytoestrogen cimicifugoside, one of the pharmacologically active ingredients of the medicinal plant Cimicifuga racemosa (black cohosh) that has been used to treat many kinds of neuronal and menopausal symptoms, such as arthritis, menopausal depression, and nerve pain. Cimicifugoside inhibited calcium increase induced by 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP), a nicotinic acetylcholine receptor (nAChR) agonist in bovine adrenal chromaffin cells with a half-maximal inhibitory concentration (IC(50)) of 18 +/- 2 microM. In contrast, cimicifugoside did not affect the calcium increases evoked by high K(+), veratridine, and bradykinin. The DMPP-induced sodium increase was also inhibited by cimicifugoside with an IC(50) of 2 +/- 0.3 microM, suggesting that the activity of nAChRs is inhibited by cimicifugoside. Cimicifugoside did not affect the KCl-induced secretion but markedly inhibited the DMPP-induced catecholamine secretion that was monitored by carbon-fiber amperometry in real time and high-performance liquid chromatography through electrochemical detection. The results suggest that cimicifugoside selectively inhibits nAChR-mediated response in bovine chromaffin cells.
Woo
Kyung-Chul
KC
Department of Life Science, Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang, South Korea.
Park
Yong-Soo
YS
Jun
Dong-Jae
DJ
Lim
Jeong-Ok
JO
Baek
Woon-Yi
WY
Suh
Byung-Sun
BS
Kim
Kyong-Tai
KT
D000311:Adrenal Glands / Q000166:cytology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D019439:Chromaffin Cells / Q000187:drug effects* / Q000378:metabolism; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects; D007810:Lanosterol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009538:Nicotine / Q000378:metabolism; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D014316:Tritium
D002395:Catecholamines; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D014316:Tritium; D007810:Lanosterol; D004246:Dimethylphenylpiperazinium Iodide; C031436:cimicifugoside; D009538:Nicotine; D012964:Sodium; D002118:Calcium