Histamine release induced by Arg-Pro-Lys-Pro(CH2)11CH3 from rat peritoneal mast cells.
The substance Arg-Pro-Lys-Pro-(CH2)11CH3 [SP1-4C12] was synthesized by forming a peptide bond between Arg-Pro-Lys-Pro, the N-terminal sequence of substance P and dodecylamine. The aim was to examine the roles of the N- and C-terminal sequences of substance P in stimulating histamine release from mast cells of the rat peritoneal cavity. SP1-4 C12 induces concentration-dependent histamine release in the range 8 to 200 nM. SP1-4C12 was 50 times more potent than substance P and 300 times more potent than dodecylamine. Unlike dodecylamine itself, SP1-4C12 induced noncytolytic histamine release which was inhibited by benzalkonium chloride and by the substance P antagonist [D-Pro4,D-Trp7,9,10]SP4-11. Histamine release induced by SP1-4C12 was inhibited at temperatures below 16 degrees C and did not require the presence of extracellular calcium ions. It is suggested that substance P and some other basic histamine liberators initiate histamine secretion by a mechanism that involves the insertion of a hydrophobic region into the membrane lipid which is necessary to present positively charged moieties to a receptor site involved in activating the secretory mechanism.
D000818:Animals; D001548:Benzalkonium Compounds / Q000494:pharmacology; D003902:Detergents / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects*; D066298:In Vitro Techniques; D007700:Kinetics; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D017830:Octoxynol; D011092:Polyethylene Glycols / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013373:Substance P / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014466:Ultraviolet Rays
D001548:Benzalkonium Compounds; D003902:Detergents; C053994:arginyl-prolyl-lysyl-prolyl-dodecane; D013373:Substance P; D011092:Polyethylene Glycols; D017830:Octoxynol