Effects of the ether phospholipid AMG-PC on mast cells are similar to that of the ether lipid AMG but different from that of the analogue hexadecylphosphocholine.
The ether lipid AMG (1-O-hexadecyl-2-O-methylglycerol) has previously been shown to have both enhancing and inhibitory effects on histamine release from isolated rat mast cells. In addition, a synergistic interaction with the phorbol ester TPA indicated protein kinase C activation. In the present investigation the effects of the related ether phospholipid AMG-PC (1-O-hexadecyl-2-O-methylglycero-3-phosphocholine) and the analogue hexadecylphosphocholine (miltefosine (HPC) are compared with those of AMG. HPC had only inhibitory effects, in contrast to AMG-PC which acted similarly on histamine release induced by compound 48/80, but had dual influence on responses to antigen and the ionophore A23187 and mainly exhibited a synergistic interaction with combinations of the ionophore and TPA. The influence of AMG-PC differed from that of AMG in some aspects whereas the character of its synergistic interaction with A23187 resembled that of AMG, in particular after pre-incubation with TPA. The results show that HPC does not share all biological activities of the antineoplastic ether lipids. They indicate that the effects of AMG-PC under appropriate conditions may be due to activation of protein kinase C but do not permit a distinction between direct effects and indirect through metabolic conversion to AMG.
Grosman
N
N
Department of Pharmacology, University of Copenhagen, Denmark.
D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects; D005995:Glyceryl Ethers / Q000494:pharmacology*; D006632:Histamine / Q000032:analysis; D006801:Humans; D066298:In Vitro Techniques; D007231:Infant, Newborn; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D010742:Phospholipid Ethers / Q000378:metabolism / Q000494:pharmacology*; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D005995:Glyceryl Ethers; D010742:Phospholipid Ethers; D010767:Phosphorylcholine; C059039:1-O-hexadecyl-2-O-methylglycerol; C039128:miltefosine; C050186:1-hexadecyl-2-methoxyglycero-3-phosphocholine; D006632:Histamine; D011493:Protein Kinase C