G-proteins as targets for non-immunological histamine releasers.
The molecular mechanism of action of several non-immunological histamine releasers has been investigated using pertussis toxin which interfers, via ADP-ribosylation, with some G-proteins. Pertussis toxin (100 ng/ml) inhibited histamine release induced by compound 48/80, substance P, mastoparan, peptide 401, bradykinin and spermine showing that a G-protein sensitive to pertussis toxin was involved in the non-immunological histamine release. All these compounds directly activate purified G-proteins. The sensitivity to pertussis toxin of this direct stimulatory effect was demonstrated for compound 48/80, mastoparan and substance P. Altogether these results suggest that a direct activation of G-protein might be the molecular mechanism of action of histamine secretagogues acting through a pertussis toxin sensitive G-protein and in this way mimic agonist-ligand receptor interaction.
Mousli
M
M
Laboratoire de Neuroimmunopharmacologie, Université Louis Pasteur Pasteur-Strasbourg I, Faculté de Pharmacie, Illkirch, France.
Bueb
J L
JL
Rouot
B
B
Landry
Y
Y
Bronner
C
C
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology*; D006636:Histamine Release / Q000187:drug effects*; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology; D010455:Peptides / Q000494:pharmacology; D037342:Pertussis Toxin; D051381:Rats; D011919:Rats, Inbred Strains; D013096:Spermine / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*; D014862:Wasp Venoms / Q000494:pharmacology; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D010566:Virulence Factors, Bordetella; D014862:Wasp Venoms; D013096:Spermine; C008331:mast cell degranulating peptide; D013373:Substance P; D003189:p-Methoxy-N-methylphenethylamine; C037500:mastoparan; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D001920:Bradykinin