DIFFERENT EFFECTS OF CINNAMIC ACID ON THE O-2 GENERATION BY GUINEA-PIG MACROPHAGES STIMULATED WITH A CHEMOTACTIC PEPTIDE AND IMMUNE-COMPLEX

Cinnamic acid inhibits the O2-generating response of guinea pig peritoneal macrophages elicited with a chemotactic peptide, N-formyl-methionyl-leucyl-phenylalanine (fMLP), but not those with ovalbumin complex of immunoglobulin G2 antibody and phorbol-myristate acetate.1) During the course of study on the inhibitory mechanism of cinnamic acid, we found that the acid also inhibited the Ca2+ mobilization elicited with fMLP, but not that with the immune complex. In addition, the treatment of macrophages with Ionomycin and ethyleneglycol bis-(βaminoethylether)-N,N'-tetra-acetic acid for depletion of the intracellular Ca2+ inactivated completely the O2 generation elicited with fMLP, but not its counterpart of the immune complex. Thus, the inhibitory activity of cinnamic acid on the O-2 generation elicited with fMLP seems partly due to that on the Ca2+ mobilization. On the other hand, cinnamic acid augmented the intracellular accumulation of adenosine 3',5'-cyclic monophosphate (cyclic AMP) in the presence of 3-isobutyl 1-methylxanthine (IBMX), and elevated more intensively the concentration of cyclic AMP when macrophages were stimulated with fMLP. Since IBMX inhibited the O-2 generation elicited with fMLP, the enhancement of activation of an adenylate cyclase by cinnamic acid might cause depression of the O-2 generation. This possibility, however, seems to be excluded by the fact that the same effect of cinnamic acid was observed even when macrophages were stimulated with the immune complex. © 1990, The Pharmaceutical Society of Japan. All rights reserved.