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.
Purcell
W M
WM
Cellular Toxicology Unit, University of Hertfordshire, Hatfield, UK. w.m.purcell@herts.ac.uk
Doyle
K M
KM
Westgate
C
C
Atterwill
C K
CK
D000818:Animals; D001665:Binding Sites / Q000502:physiology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects; D008407:Mast Cells / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D010537:Peritoneum / Q000166:cytology; D010880:Piperidines / Q000494:pharmacology; D011073:Polyamines / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013096:Spermine / Q000494:pharmacology; D013788:Thalamus / Q000166:cytology; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D018691:Excitatory Amino Acid Antagonists; D010880:Piperidines; D011073:Polyamines; D016194:Receptors, N-Methyl-D-Aspartate; D013096:Spermine; D003189:p-Methoxy-N-methylphenethylamine; D016291:Dizocilpine Maleate; C010739:ifenprodil