Abstract
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 (IC50) of 18 ± 2 μM. 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 IC50 of 2 ± 0.3 μM, 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.
Footnotes
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This work was supported by the IMT-2000 Program of the Korea Ministry of Information and Communication, the Korea Ministry of Health and Welfare, and the Brain Korea 21 Program of the Korea Ministry of Education.
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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DOI: 10.1124/jpet.103.062331.
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ABBREVIATIONS: VSCC, voltage-sensitive calcium channel; nAChR, nicotinic acetylcholine receptor; CF, cimicifugoside; DMPP, 1,1-dimethyl-4-phenylpiperazinium iodide; AM, acetoxymethyl ester; UB-165, (2-chloro-5-pyridyl)-9-azabicyclo[4.2.1]non-2-ene; DMEM, Dulbecco's modified Eagle's medium; 5-iodo-A-85380, 5-iodo-3(2(S)-azetidinylmethoxy)pyridine.
- Received November 3, 2003.
- Accepted February 2, 2004.
- The American Society for Pharmacology and Experimental Therapeutics
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