Induction of human basophil histamine release by a novel protein kinase C activator, sn-1,2-isopropylidene-3-decanoyl-glycerol (IpOCOC9): partial characterization of secretagogue characteristics.
Human leukocytes were found to release histamine at exposure for the synthetic glyceride derivative sn-1,2-isopropylidene-3-decanoyl-glycerol (IpOCOC9). The following characteristics for the IpOCOC9-induced basophil histamine release were recorded. A. In the order of 25% of the cellular histamine content was extruded at 206 mumol/l and 45% at 690 mumol/l of the compound, respectively. B. Removal of extracellular Ca2+ variably affected IpOCOC9-triggered release. C. The presence of N-ethylmaleimide (10 mumol/l) or p-bromophenacylbromide (10 mumol/l) markedly reduced IpOCOC9-induced histamine release. D. The time course of the release triggered by IpOCOC9 was intermediate to those characterizing the release triggered by 4 beta-phorbol 12-myristate 13-acetate (PMA) and by formyl-methionyl-leucyl-phenylalanine (FMLP). E. Cells desensitized to IgE-receptor-mediated stimulation were hyperresponsive to stimulation with IpOCOC9. F. Cells treated with a low concentration of 2-deoxyglucose were not hyperresponsive to IpOCOC9. These data show that IpOCOC9, a PMN/leukocyte protein kinase C stimulator, acts as a non-cytotoxic secretagogue for human basophils with a mode of action which in some, but not all respects, mimics that of PMA. In particular, IpOCOC9-triggered release resembles that reported by other authors for hyperosmolar triggering of release by mannitol.
Bergstrand
H
H
Research & Development Department, AB Draco, Lund, Sweden.
Lundquist
B
B
Michelsen
P
P
D000098:Acetophenones / Q000494:pharmacology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology; D001491:Basophils / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D003517:Cyclopentanes / Q000494:pharmacology; D003652:Decanoic Acids / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003847:Deoxyglucose / Q000494:pharmacology; D004149:Dioxoles / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005033:Ethylmaleimide / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects*; D006358:Hot Temperature; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D011961:Receptors, Fc / Q000502:physiology; D017455:Receptors, IgE; D012636:Secretory Rate / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013268:Stimulation, Chemical; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014280:Triglycerides / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D000098:Acetophenones; D000944:Antigens, Differentiation, B-Lymphocyte; D003517:Cyclopentanes; D003652:Decanoic Acids; D004149:Dioxoles; D011961:Receptors, Fc; D017455:Receptors, IgE; D014280:Triglycerides; C058204:decanoic acid cyclopentyl methyl ester; C059572:1,2-diacetyl-3-decanoylglycerol; D009240:N-Formylmethionine Leucyl-Phenylalanine; D003847:Deoxyglucose; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D005033:Ethylmaleimide; C006821:4-bromophenacyl bromide; D002118:Calcium