title: Blockade of voltage-operated calcium channels, increase in spontaneous catecholamine release and elevation of intracellular calcium levels in bovine chromaffin cells by the plant alkaloid tetrandrine.
abstract: Experiments were performed in bovine chromaffin cells in short term primary culture. Tetrandrine is a plant alkaloid from the chinese medical herb Stefania tetrandra. The aim of the present study was to investigate the mechanisms by which tetrandrine interacts with calcium signalling and to provide a quantitative description of effects. Tetrandrine blocked voltage-operated calcium channel currents concentration-dependently as shown in whole cell patch-clamp recordings. The blockade of calcium channels reduced the potassium-stimulated catecholamine release. Besides, the drug increased the spontaneous (not stimulated) release of catecholamines in the presence of extracellular calcium. Measurements of intracellular calcium levels [Ca]i showed a calcium release from intracellular stores by tetrandrine. This tetrandrine-induced [Ca]i elevation was higher in calcium containing as compared to calcium free solution. Tetrandrine effects partially overlap with those of thapsigargin, but tetrandrine has additional targets, since it increased [Ca]i in cells pretreated with thapsigargin. We conclude that tetrandrine blocks voltage-operated calcium channels and increases [Ca]i by blocking endoplasmic and other calcium pumps.
authors.affiliation: Medizinisches Institut für Umwelthygiene, Abteilung Neurotoxikologie, Düsseldorf, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Bickmeyer
authors.forename: F
authors.initials: F
authors.lastname: Weinsberg
authors.forename: E
authors.initials: E
authors.lastname: Müller
authors.forename: H
authors.initials: H
authors.lastname: Wiegand
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D044182:Benzylisoquinolines; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects*; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000187:drug effects* / Q000502:physiology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D018408:Patch-Clamp Techniques
chemical_list: D000470:Alkaloids; D044182:Benzylisoquinolines; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002395:Catecholamines; D004365:Drugs, Chinese Herbal; C009438:tetrandrine; D002118:Calcium