Exocytosis in mast cells by basic secretagogues: Evidence for direct activation of GTP-binding proteins

M. Aridor, L. M. Traub, R. Sagi-Eisenberg*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Histamine release induced by the introduction of a nonhydrolyzable analogue of GTP, GTP-γ-S, into ATP-permeabilized mast cells, is associated with phosphoinositide breakdown, as evidenced by the production of phosphatidic acid (PA) in a neomycin-sensitive process. The dependency of both PA formation and histamine secretion on GTP-γ-S concentrations is bell shaped. Whereas concentrations of up to 0.1 mM GTP-γ-S stimulate both processes, at higher concentrations the cells' responsiveness is inhibited. At a concentration of 1 mM, GTP-γ-S self-inhibits both PA formation and histamine secretion. Inhibition of secretion can, however, be overcome by the basic secretagogues compound 48/80 and mastoparan that in suboptimal dose synergize with 1 mM GTP-γ-S to potentiate secretion. Secretion under these conditions is not accompanied by PA formation and is resistant both to depletion of Ca2+ from internal stores and to pertussis toxin (PtX) treatment. In addition, 48/80, like mastoparan, is capable of directly stimulating the GTPase activity of G-proteins in a cell-free system. Together, our results are consistent with a model in which the continuous activation of a phosphoinositide-hydrolyzing phospholipase C (PLC) by a stimulatory G-protein suffices to trigger histamine secretion. Basic secretagogues of mast cells, such as compound 48/80 and mastoparan, are capable of inducing secretion in a mechanism that bypasses PLC by directly activating a G-protein that is presumably located downstream from PLC (G(E)). Thereby, these secretagogues induce histamine secretion in a receptor-independent manner.

Original languageEnglish
Pages (from-to)909-917
Number of pages9
JournalJournal of Cell Biology
Issue number3
StatePublished - 1990
Externally publishedYes


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