Ether lipid (AMG) exhibits both synergistic and inhibitory interactions with the ionophore A23187 in mast cell histamine release.
Antineoplastic ether lipids with the structure 1-O-long-chain-alkyl-2-O-methylglycero-3-phosphocholine (AMG-PC) have direct tumour cytotoxic as well as immunomodulatory effects. Their tumouricidal action has been related to protein kinase C inhibition by the dialkylglycerol metabolite (AMG). The present investigation explores the influence of AMG (1-O-hexadecyl-2-O-methyl-sn-glycerol) on histamine release from isolated rat mast cells, which have a well-characterized response to protein kinase C activators. AMG could both enhance and antagonize responses to the ionophore A23187 and to A23187 in combination with the phorbol ester TPA. The synergistic effect was maximum at 2-5 microM AMG and could increase the response to A23187 more than 10-fold. Maximal inhibitory effect was found after preincubation with 20 microM AMG, irrespective of the ionophore concentration and the presence of TPA. The synergistic effect of AMG was dependent on energy and calcium, indicating non-cytotoxic mechanisms. The interaction between AMG and A23187 resembles previous findings with TPA and suggests an activation of protein kinase C.
Grosman
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Department of Pharmacology, University of Copenhagen, Denmark.
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology*; D004347:Drug Interactions; D005995:Glyceryl Ethers / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D011919:Rats, Inbred Strains
D005995:Glyceryl Ethers; C059039:1-O-hexadecyl-2-O-methylglycerol; D000001:Calcimycin; D011493:Protein Kinase C