Protein kinase C activator phorbol 12, 13-dibutyrate inhibits platelet activating factor-stimulated Ca2+ mobilization and phosphoinositide turnover in neurohybrid NG108-15 cells.
The protein kinase C (PKC) activator, phorbol 12, 13-dibutyrate (PDBu) dose-dependently inhibited platelet-activating factor (PAF)-induced [Ca2+]i elevation and inositol monophosphate (IP1) accumulation in neurohybrid NG108-15 cells with IC50 values of 162 nM and 35 nM, respectively. Pretreatment of NG108-15 cells with PKC inhibitor H-7 partially prevented the inhibitory effect of PDBu on PAF-induced [Ca2+]i elevation as well as PI metabolism in NG108-15 cells. Pretreatment of the cells with pertussis toxin (PTX) resulted in a dose-dependent inhibition of PAF-induced IP1 and IP3 accumulation but only slightly affected PAF-induced [Ca2+]i elevation in NG108-15 cells. The results reveal that PAF receptor-mediated Ca2+ mobilization and PI metabolism in NG108-15 cells are regulated by PKC while a PTX-sensitive G protein is coupled to PAF receptor for inducing activation of phospholipase C.
Yue
T L
TL
Department of Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406-0939.
Gu
J L
JL
Feuerstein
G
G
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D004789:Enzyme Activation / Q000502:physiology; D019204:GTP-Binding Proteins / Q000502:physiology; D006822:Hybrid Cells / Q000187:drug effects / Q000378:metabolism; D037342:Pertussis Toxin; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D011493:Protein Kinase C / Q000187:drug effects* / Q000502:physiology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D010716:Phosphatidylinositols; D010972:Platelet Activating Factor; D010566:Virulence Factors, Bordetella; D015240:Phorbol 12,13-Dibutyrate; D037342:Pertussis Toxin; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D002118:Calcium