Signaling pathway in nerve growth factor induced histamine release from rat mast cells

Abstract.

Objective and Design: 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.

Materials and Methods: Isolated rat peritoneal mast cells were obtained from male Wistar rats. Histamine release was assayed spectrofl uorometrically.

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 confi rmed 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.