title: Ginsenoside-Rd from panax notoginseng blocks Ca2+ influx through receptor- and store-operated Ca2+ channels in vascular smooth muscle cells.
abstract: Previously, it was found that total saponins from panax notoginseng inhibited Ca2+ influx coupling to activation of alpha1-adrenoceptor. This study was designed to investigate the effects of ginsenoside-Rd from total saponins of panax notoginseng on receptor-operated (ROCC) and store-operated (SOCC) Ca2+ channels in vascular smooth muscle cells using fura-2 fluorescence, whole cell patch clamp ion channel recording, radio-ligand-receptor binding, 45Ca2+ radio-trace and organ bath techniques. It was found that ginsenoside-Rd reduced phenylephrine-induced contractile responses and Ca2+ influx in normal media without significant effect on these responses in Ca2+ -free media. Ginsenoside-Rd also decreased phenylephrine- and thapsigargin-induced inward Ca2+ currents, and attenuated thapsigargin- and 1-oleoy-2-acetyl-sn-glycerol (OAG)-induced cation entries that are coupled to ROCC and SOCC respectively. Ginsenoside-Rd failed to inhibit KCl-induced contraction of rat aortal rings and Ca2+ influx, and did not alter voltage-dependent inward Ca2+ current (VDCC) which was blocked by nifedipine. Also, ginsenoside-Rd did not change binding site and affinity of [3H]-prazosin for alpha1-adrenoceptor in the vascular plasma membrane. These results suggest that ginsenoside-Rd, as an inhibitor, remarkably inhibits Ca2+ entry through ROCC and SOCC without effects on VDCC and Ca2+ release in vascular smooth muscle cells.
authors.affiliation: Department of Pharmacology, Zhongshan Medical College, Sun Yat-Sen University, Guangzhou, PR China. guanyy@mail.sysu.edu.cn
authors.forename: Yong-Yuan
authors.initials: YY
authors.lastname: Guan
authors.forename: Jia-Guo
authors.initials: JG
authors.lastname: Zhou
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Guan-Lei
authors.initials: GL
authors.lastname: Wang
authors.forename: Bing-Xiang
authors.initials: BX
authors.lastname: Cai
authors.forename: Liang
authors.initials: L
authors.lastname: Hong
authors.forename: Qin-Ying
authors.initials: QY
authors.lastname: Qiu
authors.forename: Hua
authors.initials: H
authors.lastname: He
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D036145:Ginsenosides / Q000494:pharmacology*; D066298:In Vitro Techniques; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000502:physiology; D053723:Panax notoginseng / Q000737:chemistry; D010656:Phenylephrine / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D036145:Ginsenosides; D010656:Phenylephrine; D019284:Thapsigargin; D002118:Calcium; C049863:ginsenoside Rd