Chemotactic and chemoluminescent activities of substance P, substance K, kassinin and the substance P fragments SP 4-11, SP 7-11, SP 1-4 have been investigated in order to identify the minimum active molecular structure responsible for rat polymorphonuclear activation. Substance P, SP 4-11 and SP 7-11 stimulated directed locomotion (chemotaxis) and were found to be active also in the chemoluminescence assay while SP 1-4 had no effect. Moreover, all peptides, except substance K and SP 1-4, inhibited the chemotactic response of polymorphonuclears to the peptide formylmethionyl-leucyl-phenylalanine and, to a minor extent, also to leukotriene B4. A maximum of activity was observed with the C-terminal sequence SP 4-11. Substance K was found to be inactive. Kassinin exhibited a weak chemotactic effect and exerted a slight inhibition of attracting activity of peptide-formyl-methionyl-leucyl-phenylalanine. Considering that substance P and related peptides are active only at very high concentrations, it cannot be affirmed that these agents activate specific receptors. If receptors are involved, they would be of the SP-P type, since substance K is inactive.
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