Tetrandrine and transmembrane signal transduction: effect on phosphoinositide metabolism, calcium flux and protein kinase C translocation in human lymphocytes.
Time-course and dose-dependent studies showed consistent suppression of phosphoinositide turnover in Con A-stimulated human lymphocytes in the presence of the plant alkaloid, tetrandrine. Significant inhibition of Con A-stimulated calcium flux was also observed. Furthermore, protein kinase C activity was also significantly inhibited by tetrandrine irrespective of whether Con A or phorbol myristate acetate was the stimulant. These results suggest that the immunosuppressive properties of tetrandrine are in part mediated by the capacity of tetrandrine to interfere with transmembrane signalling.
Ioannoni
B
B
Department of Child Health, University of Queensland, South Brisbane, Australia.
Chalmers
A H
AH
Seow
W K
WK
McCormack
J G
JG
Thong
Y H
YH
D000470:Alkaloids / Q000494:pharmacology*; D044182:Benzylisoquinolines; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015290:Second Messenger Systems / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*
D000470:Alkaloids; D044182:Benzylisoquinolines; D015220:Calcium Channels; D007166:Immunosuppressive Agents; D010716:Phosphatidylinositols; C009438:tetrandrine; D011493:Protein Kinase C