The substance P receptor on rat mast cells and in human skin

Abstract

(D-Pro4 D- Trp7 ,9,10)SP4-11 (SPA) has been shown to be a competitive antagonist of the histamine releasing action of substance P in rat peritoneal mast cells. Antagonist activity of SPA is expressed in the concentration range 1 to 10 microM, but at higher concentrations SPA releases histamine. SPA inhibits the flare response induced by substance P in human skin but is without effect on the wheal response. Up to 12.5 pmol SPA produces neither wheal nor flare response by itself. The structurally related peptide, kassinin , does not cause histamine release from rat mast cells at concentrations up to 10 microM whereas the methyl ester of substance P was found to 1.6 times more active than substance P in this respect. The findings are discussed in terms of the classification of substance P receptors and the mechanism of wheal and flare in human skin.

The Skin as an Organ for the Study of the Pharmacology of Neuropeptides

“…However, the substance P an tagonist [Z)-Pro4,i>-Trp7-9-,0]SP4_n does act as an antagonist to substance P in human skin [17,18]. This antagonist inhibits the flare induced by substance P but does not inhibit the wheal, confirming the studies with agonists which show that substance P produces wheal and flare by an action at dif ferent sites.…”

Neuropeptides Activate Human Mast Cell Degranulation and Chemokine Production

“…44 Our results showed that substance P (4-11)[D-Pro4 D-Trp7 9] (called SP-P-T in this study), a SP antagonist, blocked SP activation of human mast cells by approximately 50% while another inhibitor, SP-Arg (spantide I), had no affect (Fig. 5).…”

Histamine Release and Local Responses of Rat and Human Skin to Substance P and Other Mammalian Tachykinins

“…Results obtained by other workers [10,31] with a series of substance P fragments and related peptides indicate clearly that the flare and wheal responses of human skin in volve, at least in part, different mechanisms. For instance, the C-terminal octapeptide, substance P-(4-11) and the nonmammalian tachykinin physalacmin produce wheal re sponses but are essentially devoid of flareinducing activity [10].…”

“…Therefore, the present observation showing that substance K, neuromedin K and kassinin which lack positively charged amino acids arc practically devoid of hista mine-releasing activity corroborate this con clusion. Several reports have emphasized the existence of a positive correlation between the histamine-releasing activity of substance P-related peptides and their ability to gen erate flare in human skin [10,31,32], Among others, we note the observation of Foreman et al [10] that pretreatment of sub jects with the HI-receptor antagonist chlor pheniramine reduces the flare responses to substance P and related peptides. The present results, showing that substance K, neurome din K and kassinin neither release histamine nor produce flare reactions in human skin are therefore in agreement with the previous findings.…”