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.