The influence of ether lipid (AMG) on histamine release from isolated rat mast cells: synergistic interaction with TPA indicates protein kinase C activation.
We have previously shown that the ether lipid AMG (1-O-hexadecyl-2-O-methyl-sn-glycerol) has both synergistic and inhibitory effects on mast cell responses to the ionophore A23187. The present investigation showed only inhibitory effects of AMG in antigen- and compound 48/80-induced histamine release. Both enhancement and inhibition were noted in responses to the combination of A23187 and the phorbol ester TPA, at 2-5 microM and 10-20 microM and 10-20 microM AMG, respectively, as found earlier with A23187 alone. The synergistic response to AMG in combination with A23187 resembles that with TPA but required higher concentrations of A23187. The flavonoid phloretin was a potent inhibitor of the response to combinations of AMG and A23187. A pronounced synergistic interaction between AMG and TPA was found at very low concentrations of A23187. Our results do not provide much information about mechanisms involved in the inhibitory effect of AMG although some competition relating to protein kinase C activity might participate. The synergistic interactions indicate that AMG can activate protein kinase C but in a manner different from the phorbol ester.
Grosman
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Department of Pharmacology, University of Copenhagen, Denmark.
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D005995:Glyceryl Ethers / Q000008:administration & dosage / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000008:administration & dosage / Q000494:pharmacology
D005995:Glyceryl Ethers; C059039:1-O-hexadecyl-2-O-methylglycerol; D000001:Calcimycin; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate