Signaling pathway in nerve growth factor induced histamine release from rat mast cells.
OBJECTIVE
We investigated a signal transduction pathway involved in NGF induced histamine secretion from mast cells. We compared this mechanism with the exocytosis induced by basic secretagogue compound 48/80.


METHODS
Isolated rat peritoneal mast cells were obtained from male Wistar rats. Histamine release was assayed spectrofluorometrically.


RESULTS
We found that tyrosine kinase inhibitor genistein, phospholipase C (PLC) inhibitor U-73122, phosphatidylinositol 3-kinase (PI-3 kinase) inhibitor wortmannin, protein kinase C (PKC) inhibitors, staurosporine and GF109203X, but not MAP kinase inhibitors, SB203580 and PD98059, reduce histamine secretion in NGF provoked mast cell degranulation. In compound 48/80 mediated degranulation, we confirmed only the involvement of tyrosine kinase and PLC, but not PI-3 kinase, PKC and MAP kinases.


CONCLUSIONS
Our results indicate that release of histamine from mast cells after stimulation with NGF is regulated by tyrosine kinase, PLC, PI-3 kinase and PKC, but not by MAP kinases. This biochemical pathway differs from that provoked by compound 48/80.
Stempelj
M
M
Department of Pharmacology and Experimental Toxicology, Faculty of Medicine, University of Ljubljana, Korytkova 2, 1000 Ljubljana, Slovenia. mateja.stempelj@mf.uni-lj.si
Ferjan
I
I
D000704:Analysis of Variance; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006632:Histamine / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D008407:Mast Cells / Q000378:metabolism*; D008954:Models, Biological; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011725:Pyridines / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D019311:Staurosporine / Q000494:pharmacology; D014443:Tyrosine / Q000378:metabolism; D000077191:Wortmannin; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000730:Androstadienes; D004791:Enzyme Inhibitors; D004963:Estrenes; D005419:Flavonoids; D007093:Imidazoles; D007211:Indoles; D008301:Maleimides; D011725:Pyridines; D011760:Pyrrolidinones; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D014443:Tyrosine; D006632:Histamine; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D048051:p38 Mitogen-Activated Protein Kinases; D019311:Staurosporine; C070515:bisindolylmaleimide I; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D000077191:Wortmannin