14-deoxyandrographolide as a platelet activating factor antagonist in bovine neutrophils.
14-Deoxyandrographolide (14-DAP) is a labdane diterpene isolated from Andrographis paniculata with previously reported calcium channel blocking activity. Its potential platelet activating factor (PAF) antagonistic activity in bovine neutrophils was assessed. 14-DAP, in concentrations between 10-100 microM, reduced the extracellular acidification rate and the intracellular alkalinization in a dose-dependent manner. In addition, 14-DAP reduced PAF-induced calcium flux in the presence of extracellular calcium, and tyrosine phosphorylation of a 44 kDa protein corresponding to the MAPK(ERK1). However, 14-DAP reduced the 3H-PAF binding with a Ki of 7.8 x 10 (- 9)M, and a Hill slope of 0.63, suggesting that there is more than one binding site for 14-DAP. We concluded that 14-DAP is an effective antagonist of PAF-mediated processes in bovine neutrophils, probably by virtue of its calcium channel blocking property.
Burgos
Rafael A
RA
Laboratory of Molecular Pharmacology, Institute of Pharmacology, Facultad de Ciencias Veterinarias, Universidad Austral de Chile, Valdivia, Chile. rburgos1@uach.cl
Hidalgo
María A
MA
Monsalve
Juan
J
LaBranche
Timothy P
TP
Eyre
Peter
P
Hancke
Juan L
JL
D035685:Andrographis; D000818:Animals; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D002417:Cattle; D004224:Diterpenes / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D008517:Phytotherapy; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*
C114791:14-deoxyandrographolide; D002121:Calcium Channel Blockers; D004224:Diterpenes; D010972:Platelet Activating Factor; D020928:Mitogen-Activated Protein Kinases