Role of the N-terminal arginine in the histamine-releasing activity of substance P, bradykinin and related peptides.
A series of substance P (SP)- and bradykinin (BK)-related peptides have been compared for their histamine-releasing activities on rat peritoneal mast cells. Some of these peptides only differed in the N-acetylation of the N-terminal arginine residue or by the removal of charged residue at the N-terminal. The aim was to examine the role of the N-terminal positive charges in the histamine-releasing activity of compounds that are selective for the SP receptor (named NK-1) or for the B2 type bradykinin receptor. Only compounds with positive charges at the N-terminal caused non-cytotoxic histamine release from rat mast cells. It is suggested that SP- and BK-related peptides caused histamine release by a mechanism which appeared to be non-specific and not related to the activation of mast cell NK-1 or B2 receptors, respectively. Our results show that NK-1 agonists or B2 antagonists devoid of histamine-releasing activity, which could be of potential use in the clinic, can be obtained by removing the positively charged N-terminal aminoacids or by N-acetylation of the N-terminal arginine.
Devillier
P
P
Laboratoire d'Immunologie, Centre Hospitalier Universitaire Cochin Port-Royal, Paris, France.
Drapeau
G
G
Renoux
M
M
Regoli
D
D
D000818:Animals; D001120:Arginine / Q000502:physiology*; D006636:Histamine Release / Q000187:drug effects*; D066298:In Vitro Techniques; D007705:Kinins / Q000494:pharmacology; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism; D009479:Neuropeptides / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology*
D007705:Kinins; D009479:Neuropeptides; D013373:Substance P; D001120:Arginine