Nerve growth factor (NGF) receptors on mast cells: effects of the cholinergic neurotoxin ethylcholine mustard aziridinium ion (ECMA).

The effects of nerve growth factor (NGF) on rat peritoneal mast cells were studied as a model for delineating the potential actions of the cholinergic neurotoxin ethyl choline mustard aziridinium (ECMA) on cholinergic neuronal NGF receptors. Both NGF and compound 48/80 (a polycationic secretagogue) were used to induce histamine release from a mixed population of rat peritoneal cells in vitro. NGF induced a dose-dependent release of up to 80% of the total cellular content (160% of endogenous release) in the presence of L-alpha-phosphatidyl serine (10 micrograms/ml) at concentrations of 0.1-10 micrograms/ml. Compound 40/80 also elicited comparable release of histamine over a concentration range of 1-10 micrograms/ml. ECMA had no effect on endogenous histamine release and was also shown to partially block the NGF induced histamine release at a concentration of 6 microM and 12.5 microM, and significantly at 50 microM (50 microM blocking up to 60% of the release). ECMA did not affect the 48/80 induced release. However, preincubation of the cells with ECMA (2 hr 37 degrees C) followed by replacement with fresh medium did not affect NGF induced histamine release. This suggests that although ECMA can alkylate NGF it probably does not inactivate the receptor in this peripheral model. Ouabain (1-10 mM) decreased histamine release by 25% supporting the proposed links between NGF receptor mediated events in neurones and the sodium pump.