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Article: Dual effects of tetrandrine on cytosolic calcium in human leukaemic HL-60 cells: intracellular calcium release and calcium entry blockade

TitleDual effects of tetrandrine on cytosolic calcium in human leukaemic HL-60 cells: intracellular calcium release and calcium entry blockade
Authors
KeywordsTetrandrine
Thapsigarin
Hernandezine
Calcium antagonist
Cytosolic calciium
Issue Date1994
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/bjp
Citation
British Journal of Pharmacology, 1994, v. 113, p. 767-774 How to Cite?
Abstract1. Tetrandrine (TET, a Ca2+ antagonist of Chinese herbal origin) and thapsigargin (TSG, an endoplasmic reticulum Ca2+ pump inhibitor) concentration-dependently mobilized Ca2+ from intracellular stores of HL-60 cells, with EC50 values of 20 microM and 0.8 nM, respectively. After intracellular Ca2+ release by 30 nM TSG, there was no more discharge of Ca2+ by TET (100 microM), and vice versa. 2. Pretreatments with 100 nM rauwolscine (alpha 2-adrenoceptor antagonist), 100 nM prazosin (alpha 1-adrenoceptor antagonist), 10 nM phorbol myristate acetate (PMA, a protein kinase C activator) or 100 nM staurosporine (a protein kinase C inhibitor) had no effect on 100 microM TET-induced intracellular Ca2+ release. 3. After intracellular Ca2+ release by 30 nM TSG in Ca(2+)-free medium, readmission of Ca2+ caused a substantial and sustained extracellular Ca2+ entry. The latter was almost completely inhibited by 100 microM TET (IC50 of 20 microM) added just before Ca2+ readmission. In Ca(2+)-containing medium, 30 nM TSG caused a sustained phase of cytosolic Ca2+ elevation, which could be abolished by 100 microM TET. TET was also demonstrated to retard basal entry of extracellular Mn2+ and completely inhibit TSG-stimulated extracellular Mn2+ entry. 4. TSG-induced extracellular Ca2+ entry was insensitive to the L-type Ca2+ channel blocker, nifedipine (1 microM), but was completely inhibited by the non-selective Ca2+ channel blocker La3+ (300 microM). Depolarization with 100 mM KCl did not raise the cytosolic Ca2+ level. 5. These data suggest that (a) TET and TSG mobilized the same Ca2+ pool and TET-induced intracellular Ca2+ release was independent of protein kinase C activity and alpha-adrenoceptor activation, and (b) TET blocked the voltage-insensitive Ca2+ entry pathway activated by TSG. These dual effects on HL-60 cells were also observed with hernandezine (HER), a TET-like compound and in another cell type, murine B lymphoma M12.4 cells.
Persistent Identifierhttp://hdl.handle.net/10722/49295
ISSN
2023 Impact Factor: 6.8
2023 SCImago Journal Rankings: 2.119
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLeung, YMen_HK
dc.contributor.authorKwan, CYen_HK
dc.contributor.authorLoh, TTen_HK
dc.date.accessioned2008-06-12T06:38:45Z-
dc.date.available2008-06-12T06:38:45Z-
dc.date.issued1994en_HK
dc.identifier.citationBritish Journal of Pharmacology, 1994, v. 113, p. 767-774en_HK
dc.identifier.issn0007-1188en_HK
dc.identifier.urihttp://hdl.handle.net/10722/49295-
dc.description.abstract1. Tetrandrine (TET, a Ca2+ antagonist of Chinese herbal origin) and thapsigargin (TSG, an endoplasmic reticulum Ca2+ pump inhibitor) concentration-dependently mobilized Ca2+ from intracellular stores of HL-60 cells, with EC50 values of 20 microM and 0.8 nM, respectively. After intracellular Ca2+ release by 30 nM TSG, there was no more discharge of Ca2+ by TET (100 microM), and vice versa. 2. Pretreatments with 100 nM rauwolscine (alpha 2-adrenoceptor antagonist), 100 nM prazosin (alpha 1-adrenoceptor antagonist), 10 nM phorbol myristate acetate (PMA, a protein kinase C activator) or 100 nM staurosporine (a protein kinase C inhibitor) had no effect on 100 microM TET-induced intracellular Ca2+ release. 3. After intracellular Ca2+ release by 30 nM TSG in Ca(2+)-free medium, readmission of Ca2+ caused a substantial and sustained extracellular Ca2+ entry. The latter was almost completely inhibited by 100 microM TET (IC50 of 20 microM) added just before Ca2+ readmission. In Ca(2+)-containing medium, 30 nM TSG caused a sustained phase of cytosolic Ca2+ elevation, which could be abolished by 100 microM TET. TET was also demonstrated to retard basal entry of extracellular Mn2+ and completely inhibit TSG-stimulated extracellular Mn2+ entry. 4. TSG-induced extracellular Ca2+ entry was insensitive to the L-type Ca2+ channel blocker, nifedipine (1 microM), but was completely inhibited by the non-selective Ca2+ channel blocker La3+ (300 microM). Depolarization with 100 mM KCl did not raise the cytosolic Ca2+ level. 5. These data suggest that (a) TET and TSG mobilized the same Ca2+ pool and TET-induced intracellular Ca2+ release was independent of protein kinase C activity and alpha-adrenoceptor activation, and (b) TET blocked the voltage-insensitive Ca2+ entry pathway activated by TSG. These dual effects on HL-60 cells were also observed with hernandezine (HER), a TET-like compound and in another cell type, murine B lymphoma M12.4 cells.en_HK
dc.format.extent388 bytes-
dc.format.mimetypetext/html-
dc.languageengen_HK
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/bjpen_HK
dc.subjectTetrandrineen_HK
dc.subjectThapsigarinen_HK
dc.subjectHernandezineen_HK
dc.subjectCalcium antagonisten_HK
dc.subjectCytosolic calciiumen_HK
dc.titleDual effects of tetrandrine on cytosolic calcium in human leukaemic HL-60 cells: intracellular calcium release and calcium entry blockadeen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0007-1188&volume=113&spage=767&epage=774&date=1994&atitle=Dual+effects+of+tetrandrine+on+cytosolic+calcium+in+human+leukaemic+HL-60+cells:+intracellular+calcium+release+and+calcium+entry+blockadeen_HK
dc.identifier.emailKwan, CY: cykwan@hkucc.hku.hken_HK
dc.identifier.emailLoh, TT: ttloh@hkucc.hku.hken_HK
dc.description.naturepublished_or_final_versionen_HK
dc.identifier.doi10.1111/j.1476-5381.1994.tb17059.x-
dc.identifier.pmid7858865-
dc.identifier.pmcidPMC1510437en_HK
dc.identifier.scopuseid_2-s2.0-0028127268-
dc.identifier.hkuros3093-
dc.identifier.isiWOS:A1994PN23700019-
dc.identifier.issnl0007-1188-

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