C-terminal substance P fragments elicit histamine release from a murine mast cell line.
Incubation of mouse mast cells with C-terminal substance P fragments in the micromolar range caused a release of histamine. Maximum release was observed with the tetrapeptide SP(8-11), followed by the tripeptide SP(9-11). SP(6-11) and SP(5-11) were nearly equipotent, while SP(4-11) caused only a slight histamine release. The substance P parent molecule and the N-terminal substance P fragments SP(1-4), SP(1-6) and SP(1-7) evoked no release of histamine. In confirmation of our previous findings, incubation with neurokinin A caused a release comparable to that of SP(8-11). Whereas neurokinin A-induced release was partially preventable by pretreating the cells with the NK2 receptor-selective antagonist cyclo(Gln-Trp-Phe-(R)Gly[ANC-2]Leu-Met), SP(8-11)-induced release was completely abolished by such treatment. The results provide the first evidence for the involvement of NK2 tachykinin receptors in the release of histamine by C-terminal substance P fragments.
Krumins
S A
SA
Biochemical Pharmacology Branch, United States Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland 21010.
Broomfield
C A
CA
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D006636:Histamine Release / Q000187:drug effects*; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology*; D013373:Substance P / Q000494:pharmacology*
D010446:Peptide Fragments; D013373:Substance P