title: Ionic mechanisms of tetrandrine in cultured rat aortic smooth muscle cells.
abstract: The ionic mechanism of tetrandrine, an alkaloid extracted from the Chinese medicinal herb Radix stephania tetrandrae, was investigated in A7r5 vascular smooth muscle cells. The nystatin-perforated whole-cell voltage-clamp technique was performed to examine the effects of tetrandrine on ionic currents. Tetrandrine (1-100 microM) reversibly caused an inhibition of L-type voltage-dependent Ca2+ current (I(Ca,L)) in a concentration-dependent manner. Tetrandrine did not cause any change in the overall shape of the current-voltage relationship of I(Ca,L). The IC50 value of tetrandrine-induced inhibition of I(Ca,L) was 5 microM. In the presence of Bay K 8644 (3 microM) or cyclopiazonic acid (30 microM), tetrandrine still produced a significant inhibition of I(Ca,L). The inhibitory effects of tetrandrine on I(Ca,L) exhibited tonic and use-dependent characteristics. Moreover. tetrandrine (3 microM) shifted the steady-state inactivation curve of I(Ca,L) to more negative membrane potentials by approximately -15 mV. These results indicate that tetrandrine directly inhibits the voltage-dependent L-type Ca2+ current in vascular smooth muscle cells, which may predominantly contribute to the vasodilatory actions of tetrandrine.
authors.affiliation: Department of Medical Education and Research, Veterans General Hospital-Kaohsiung, Kaohsiung City, Taiwan. snwu@isca.vghks.gov.tw
authors.forename: S N
authors.initials: SN
authors.lastname: Wu
authors.forename: T L
authors.initials: TL
authors.lastname: Hwang
authors.forename: C R
authors.initials: CR
authors.lastname: Jan
authors.forename: C J
authors.initials: CJ
authors.lastname: Tseng
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D044182:Benzylisoquinolines; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D051381:Rats
chemical_list: D000470:Alkaloids; D044182:Benzylisoquinolines; D002121:Calcium Channel Blockers; D015220:Calcium Channels; C009438:tetrandrine