INTERACTION OF NEUROTENSIN WITH THE SUBSTANCE P RECEPTOR MEDIATING HISTAMINE RELEASE FROM RAT MAST CELLS AND THE FLARE IN HUMAN SKIN

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Abstract
1 Substance P induced histamine release from rat peritoneal mast cells in a dose-dependent manner over the concentration range 1 to 10 μm. 2 At concentrations in the range 2.5 to 10 μm, neurotensin produced only about 5% release of histamine, which was substantially less than the maximum effect obtained with substance P. 3 Neurotensin, 2.5 to 10 μm produced graded inhibition of histamine release induced by substance P. The inhibitory effect of neurotensin was not seen when histamine release was induced by an antigen-antibody reaction or by the ionophore, A 23187. Some evidence was obtained to suggest that compound 48/80 may interact with the same receptor as substance P and neurotensin. 4 [d-Arg8]neurotensin, [d-Arg9]neurotensin, xenopsin and the C-terminal octapeptide of substance P (SP4–11) all inhibited histamine release by substance P, but physalaemin did not. 5 Neurotensin inhibited the wheal and flare reactions induced by substance P in human skin. 6 [d-Trp7,9]substance P released histamine from rat mast cells and was about 12 times more potent than substance P itself. [d-Trp7,9]SP1–11 also produced wheal and flare responses in human skin, being 1.8 times more potent than substance P in the production of flare.