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. 1987 Nov;92(3):597–601. doi: 10.1111/j.1476-5381.1987.tb11361.x

The actions of inhibitors of diacylglycerol kinase and diacylglycerol lipase on histamine release from rat peritoneal mast cells.

M E Cantwell 1, J C Foreman 1
PMCID: PMC1853701  PMID: 2447987

Abstract

1. RHC 80267 and R59 022 are selective inhibitors of diacylglycerol (DAG) lipase and DAG kinase enzymes respectively. These inhibitors were examined with regard to their effects on oleoylacetylglycerol (OAG)-and anti-IgE- induced histamine secretion in rat peritoneal mast cells. 2. RHC 80267, 10 microM and R59 022, 50 microM both enhanced OAG-induced histamine release by 30% and 40% respectively. 3. In the concentration range 3-30 microM, R59 022 enhanced anti-IgE-induced histamine release by up to about 40%, whereas RHC 80267 was without effect. 4. The enhancement of anti-IgE-induced histamine release by R59 022 is consistent with a role for protein kinase C in transducing immunological signals to rat peritoneal mast cells. 5. The lack of effect of RHC 80267 in this situation may indicate that in the mast cell, DAG kinase is more active than DAG lipase in degrading physiological levels of DAG.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Beaven M. A., Moore J. P., Smith G. A., Hesketh T. R., Metcalfe J. C. The calcium signal and phosphatidylinositol breakdown in 2H3 cells. J Biol Chem. 1984 Jun 10;259(11):7137–7142. [PubMed] [Google Scholar]
  2. Blumberg P. M. In vitro studies on the mode of action of the phorbol esters, potent tumor promoters, part 2. Crit Rev Toxicol. 1981 Jun;8(3):199–234. doi: 10.3109/10408448109109658. [DOI] [PubMed] [Google Scholar]
  3. Cantwell M. E., Foreman J. C. Characteristics of the effect of phorbol ester on rat mast cells: interaction with anti-IgE. Agents Actions. 1986 Apr;18(1-2):77–80. doi: 10.1007/BF01987988. [DOI] [PubMed] [Google Scholar]
  4. Cantwell M. E., Foreman J. C. Phorbol esters induce a slow, non-cytotoxic release of histamine from rat peritoneal mast cells. Agents Actions. 1987 Apr;20(3-4):165–168. doi: 10.1007/BF02074658. [DOI] [PubMed] [Google Scholar]
  5. Castagna M., Takai Y., Kaibuchi K., Sano K., Kikkawa U., Nishizuka Y. Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters. J Biol Chem. 1982 Jul 10;257(13):7847–7851. [PubMed] [Google Scholar]
  6. Heiman A. S., Crews F. T. Characterization of the effects of phorbol esters on rat mast cell secretion. J Immunol. 1985 Jan;134(1):548–555. [PubMed] [Google Scholar]
  7. Katakami Y., Kaibuchi K., Sawamura M., Takai Y., Nishizuka Y. Synergistic action of protein kinase C and calcium for histamine release from rat peritoneal mast cells. Biochem Biophys Res Commun. 1984 Jun 15;121(2):573–578. doi: 10.1016/0006-291x(84)90220-1. [DOI] [PubMed] [Google Scholar]
  8. Kawahara Y., Takai Y., Minakuchi R., Sano K., Nishizuka Y. Phospholipid turnover as a possible transmembrane signal for protein phosphorylation during human platelet activation by thrombin. Biochem Biophys Res Commun. 1980 Nov 17;97(1):309–317. doi: 10.1016/s0006-291x(80)80169-0. [DOI] [PubMed] [Google Scholar]
  9. Muid R. E., Penfield A., Dale M. M. The diacylglycerol kinase inhibitor, R59022, enhances the superoxide generation from human neutrophils induced by stimulation of fMet-Leu-Phe, IgG and C3b receptors. Biochem Biophys Res Commun. 1987 Mar 13;143(2):630–637. doi: 10.1016/0006-291x(87)91400-8. [DOI] [PubMed] [Google Scholar]
  10. Nishizuka Y. Studies and perspectives of protein kinase C. Science. 1986 Jul 18;233(4761):305–312. doi: 10.1126/science.3014651. [DOI] [PubMed] [Google Scholar]
  11. Nishizuka Y. The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature. 1984 Apr 19;308(5961):693–698. doi: 10.1038/308693a0. [DOI] [PubMed] [Google Scholar]
  12. Sagi-Eisenberg R., Foreman J. C., Raval P. J., Cockcroft S. Protein and diacylglycerol phosphorylation in the stimulus-secretion coupling of rat mast cells. Immunology. 1987 Jun;61(2):203–206. [PMC free article] [PubMed] [Google Scholar]
  13. Sagi-Eisenberg R., Mazurek N., Pecht I. Ca2+ fluxes and protein phosphorylation in stimulus-secretion coupling of basophils. Mol Immunol. 1984 Dec;21(12):1175–1181. doi: 10.1016/0161-5890(84)90007-5. [DOI] [PubMed] [Google Scholar]
  14. Sagi-Eisenberg R., Pecht I. Protein kinase C, a coupling element between stimulus and secretion of basophils. Immunol Lett. 1984;8(5):237–241. doi: 10.1016/0165-2478(84)90002-6. [DOI] [PubMed] [Google Scholar]
  15. Sutherland C. A., Amin D. Relative activities of rat and dog platelet phospholipase A2 and diglyceride lipase. Selective inhibition of diglyceride lipase by RHC 80267. J Biol Chem. 1982 Dec 10;257(23):14006–14010. [PubMed] [Google Scholar]
  16. de Chaffoy de Courcelles D. C., Roevens P., Van Belle H. R 59 022, a diacylglycerol kinase inhibitor. Its effect on diacylglycerol and thrombin-induced C kinase activation in the intact platelet. J Biol Chem. 1985 Dec 15;260(29):15762–15770. [PubMed] [Google Scholar]

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