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

Abstract

Substance P and two recently identified neurokinins, substance K and neuromedin K as well as the nonmammalian tachykinin kassinin were compared for (a) histamine-releasing abilities from rat mast cells, (b) plasma extravasation effects on rat skin, and (c) wheal and flare responses on human skin. Among the four tachykinins, a significantly dose-dependent histamine release from rat mast cells and a flare response in human skin was observed only with substance P, indicating the possible implication of histamine in this response. On the other hand, the four peptides were similarly active on the wheal response (plasma extravasation produced by increased permeability of capillaries and venules) in human skin and on the plasma extravasation in the rat skin, suggesting a dissociation of effects and possibly of receptors.

Profile of capsaicin‐induced mouse ear oedema as neurogenic inflammatory model: comparison with arachidonic acid‐induced ear oedema

“…Furthermore, our studies confirmed that the synergistic effect of neuropeptides such as CGRP and SP in fmol could be participating in the development of ear oedema. Neuropeptides have been reported to release histamine from mast cells (Piotrowski & Foreman, 1985;Devillier et al, 1986), but capsaicin did not cause histamine release from mast cells directly (data not shown). Additionally, mast cells are numerous around blood vessels and nerves (Nilsson et al, 1990); this is further support for the suggestion that the neuropeptides evoked by capsaicin through activation of sensory nerves are able to release histamine (and 5-HT) from mast cells as the chemical mediator, and this response is an essential pathway in the development of capsaicin-induced ear oedema.…”

Interactions between the tachykinins and calcitonin gene‐related peptide lead to the modulation of oedema formation and blood flow in rat skin

“…Both neurokinin A (substance K) and neurokinin B (neuromedin K) were extracted from mammalian spinal cord (Kimura et al, 1983;Kangawa et al, 1983;Minamino et al, 1984). Like substance P, neurokinin A and neurokinin B increase microvascular permeability causing local oedema formation when injected into rat skin (Gamse & Saria, 1985) and human skin (Devillier et al, 1986;Fuller et al, 1987). The tachykinins do not possess a common N-terminus (see Table 1) and the neurokinins are >50 times less potent than substance P in stimulating histamine release from rat peritoneal mast cells (Devillier et al, 1986).…”

“…Like substance P, neurokinin A and neurokinin B increase microvascular permeability causing local oedema formation when injected into rat skin (Gamse & Saria, 1985) and human skin (Devillier et al, 1986;Fuller et al, 1987). The tachykinins do not possess a common N-terminus (see Table 1) and the neurokinins are >50 times less potent than substance P in stimulating histamine release from rat peritoneal mast cells (Devillier et al, 1986). This suggests that oedema formation induced by the neurokinins is not mediated through histamine release from mast cells.…”

Sensory neuropeptide effects in human skin

“…Tachykinins, with a similar structure to SP, neurokin-ins A (NKA) (Pernow, 1985) and B (NKB) (Laufer et al, 1985) have been discovered in the mammalian nervous system and may also be present in cutaneous sensory nerves, so that their release may also contribute to the wheal and distant flare response (Pernow, 1985). SP has been shown to produce a wheal and distant flare response via the release of histamine from skin mast cells (Hagermark et al, Fewtrell et al, 1982;Foreman et al, 1983;Saria et al, 1983;Barnes et al, 1986;Devillier et al, 1986) and cause vasodilatation through release of cyclo-oxygenase products . It is not yet certain whether all the skin sensory neuropeptides act similarly via the secondary release of vasoactive substances, such as histamine or cyclo-oxygenase products.…”