PMID- 1330596 OWN - NLM STAT- MEDLINE DCOM- 19921127 LR - 20190623 IS - 0014-2999 (Print) IS - 0014-2999 (Linking) VI - 218 IP - 2-3 DP - 1992 Aug 6 TI - Arachidonic acid release and platelet-activating factor formation by staurosporine in human neutrophils challenged with n-formyl peptide. PG - 251-8 AB - Staurosporine, a putative protein kinase C (PKC) inhibitor, increased the release of [14C]arachidonic acid dose dependently between 100 nM and 1000 nM in human neutrophils challenged with 100 nM N-formyl-methionine-leucine-phenylalanine (FMLP). Staurosporine also increased the formation of leukotriene B4 (LTB4) and platelet-activating factor (PAF) in a dose-dependent manner. In addition, exogenously added lyso-PAF further augmented [3H]PAF formation in staurosporine-pretreated human neutrophils stimulated by FMLP, thus suggesting an activation of acetyl-CoA: lyso-PAF acetyltransferase by staurosporine. The potentiation of [14C]arachidonic acid release and [3H]PAF formation by staurosporine was further enhanced in the presence of 100 nM phorbol 12-myristate 13-acetate (PMA), which pinpoints a mechanism other than the modulation of PKC in this process, inasmuch as staurosporine antagonizes PMA-induced O2- production and [3H]PAF formation. Additional studies with other putative PKC inhibitors also revealed the potentiating effects of 1-(5-isoquinolinsulfonyl)-2-methylpiperazine (H-7, 20 microM) and sphingosine (2.5 microM) on FMLP-induced [14C]arachidonic acid release and [3H]PAF formation. We therefore conjecture that staurosporine-sensitive protein kinases including PKC are not involved in the activation of phospholipase A2 and acetyl-CoA:lyso-PAF acetyltransferase. FAU - Muller, S AU - Muller S AD - Department of Gynecology, Universitatsklinikum Steglitz, Free University Berlin, Germany. FAU - Nigam, S AU - Nigam S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Alkaloids) RN - 0 (Platelet Activating Factor) RN - 1HGW4DR56D (Leukotriene B4) RN - 27YG812J1I (Arachidonic Acid) RN - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine) RN - EC 2.7.11.13 (Protein Kinase C) RN - EC 3.1.1.32 (Phospholipases A) RN - EC 3.1.1.4 (Phospholipases A2) RN - H88EPA0A3N (Staurosporine) SB - IM MH - Alkaloids/*pharmacology MH - Arachidonic Acid/*metabolism MH - Dose-Response Relationship, Drug MH - Humans MH - In Vitro Techniques MH - Leukotriene B4/biosynthesis MH - N-Formylmethionine Leucyl-Phenylalanine/pharmacology MH - Neutrophils/*drug effects/metabolism MH - Phospholipases A/metabolism MH - Phospholipases A2 MH - Platelet Activating Factor/*biosynthesis MH - Protein Kinase C/*antagonists & inhibitors MH - Staurosporine EDAT- 1992/08/06 00:00 MHDA- 1992/08/06 00:01 CRDT- 1992/08/06 00:00 PHST- 1992/08/06 00:00 [pubmed] PHST- 1992/08/06 00:01 [medline] PHST- 1992/08/06 00:00 [entrez] AID - 0014-2999(92)90176-5 [pii] AID - 10.1016/0014-2999(92)90176-5 [doi] PST - ppublish SO - Eur J Pharmacol. 1992 Aug 6;218(2-3):251-8. doi: 10.1016/0014-2999(92)90176-5.