Molecular basis for cellular effects of naturally occurring polyamines.
The naturally occurring polyamines, putrescine, spermidine and spermine, and the analogue cadaverine, induce a dose-dependent histamine release from rat peritoneal mast cells. Spermine was the most active among these polycationic metabolites, followed by spermidine and putrescine. The histamine release was inhibited by a 2 h pretreatment of the cells with pertussis toxin (100 ng/ml), demonstrating the involvement of a pertussis toxin-sensitive GTP-binding regulatory protein during the exocytotic process. Experiments performed with purified Go/Gi proteins reconstituted into phospholipid vesicles showed a direct stimulation of GTPase activity by the polyamines. This direct stimulation of G proteins and the consequent activation of the coupled effectors may represent a new mechanism of action for natural polyamines controlling receptor-dependent processes.
Bueb
J L
JL
Laboratoire de Neuroimmunopharmacologie, Université Louis Pasteur, Strasbourg I, Faculté de Pharmacie, Illkirch, France.
Mousli
M
M
Landry
Y
Y
D000818:Animals; D002103:Cadaverine / Q000494:pharmacology; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000502:physiology; D006636:Histamine Release / Q000187:drug effects*; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*; D010529:Peritoneal Cavity / Q000166:cytology; D037342:Pertussis Toxin; D011073:Polyamines / Q000494:pharmacology*; D011700:Putrescine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013095:Spermidine / Q000494:pharmacology; D013096:Spermine / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D011073:Polyamines; D010566:Virulence Factors, Bordetella; D013096:Spermine; D037342:Pertussis Toxin; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D002103:Cadaverine; D013095:Spermidine; D011700:Putrescine