CHARACTERIZATION 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) rece ptors by binding to a specific polyamine site associated with a NMDA r eceptor macrocomplex. Polyamines induce histamine release from mast ce lls, although the mechanism had not been defined. We have examined whe ther spermine, a natural polyamine, and compound 48/80, regarded as a synthetic polyamine, activate mast cells by a polyamine site associate d with a NMDA receptor macrocomplex. Spermine induced secretion of his tamine from rat peritoneal mast cells and rat brain mast cells in a co ncentration-dependent manner. Kat 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 his tamine secretion from mast cells exposed to polyamines; the percentage inhibition was greater against spermine than compound 48/80. These da ta support the proposal that spermine (and possibly compound 48/80) in duce histamine release from mast cells by interacting with a specific polyamine site on a NMDA receptor complex.