Characterisation of a functional polyamine site on rat mast cells: association with a NMDA receptor macrocomplex

Polyamines can modulate activation of N-methyl- d-aspartate (NMDA) receptors by binding to a specific polyamine site associated with a NMDA receptor macrocomplex. Polyamines induce histamine release from mast cells, although the mechanism had not been defined. We have examined whether spermine, a natural polyamine, and compound 48 80 , regarded as a synthetic polyamine, activate mast cells by a polyamine site associated with a NMDA receptor macrocomplex. Spermine induced secretion of histamine from rat peritoneal mast cells and rat brain mast cells in a concentration-dependent manner. Rat peritoneal mast cells were used as a model system to explore the effects of NMDA antagonists on polyamine-induced histamine release. Ifenprodil, MK801 and arcaine inhibited histamine secretion from mast cells exposed to polyamines; the percentage inhibition was greater against spermine than compound 48 80 . These data support the proposal that spermine (and possibly compound 48 80 ) induce histamine release from mast cells by interacting with a specific polyamine site on a NMDA receptor complex.