Characterization of neuropeptide‐induced histamine release from human dispersed skin mast cells

Abstract

1 Human skin mast cells, unlike other human mast cells so far studied, released histamine in a concentration-related manner in response to substance P, vasoactive intestinal peptide (VIP) and somatostatin (1 yM to 30 yM). In contrast, eledoisin, physalaemin, neurokinin A, neurokinin B, calcitonin gene-related peptide (CGRP), neurotensin, bradykinin and Lys-bradykinin induced negligible histamine release. 2 The low histamine releasing activity of physalaemin, eledoisin, neurokinin A and neurokinin B relative to substance P suggests that the human skin mast cell activation site is distinct from the tachykinin NK-1, NK-2 or NK-3 receptors described in smooth muscle.3 The relative potencies of substance P and its fragments SP2 11, SP3 11, SP4_11 and SP1,4 in releasing histamine from human skin mast cells suggests that both the basic N-terminal amino acids and the lipophilic C-terminal portion of substance P are essential for activity. 4 Peptide-induced histamine release, like that induced by compound 48/80, morphine and poly-Llysine, is rapid, reaching completion in 10-20s, is largely independent of extracellular calcium but requires intact glycolysis and oxidative phosphorylation. The substance P analogue, [D-Pro4,D-Trp7'9 "0] SP411 (SPA), not only reduced substance Pinduced histamine release in a concentration-related manner but also inhibited that induced by VIP, somatostatin, compound 48/80, poly-L-lysine and morphine but not anti-IgE. 6 The similar characteristics of histamine release induced by substance P. VIP, somatostatin, compound 48/80, poly-L-lysine and morphine suggest that they share a common pathway of activationsecretion coupling distinct from that of IgE-dependent activation. Furthermore, the ability of human skin mast cells to respond to basic non-immunological stimuli including neuropeptides may reflect a specialised function for these cells.

Chronic psychological stress enhances nociceptive processing in the urinary bladder in high-anxiety rats

“…These stress-induced morphological changes are prevented by central and peripheral administration of an NK-1 receptor antagonist. Together with the observations that mast cells are closely apposed to SP-containing nerve terminals and that mast cell secretion is elicited by SP [26,32,33], this evidence suggests that stress-induced release of SP may induce morphological changes in the bladder wall that are characteristic of IC.…”

Endothelin‐1 induces a histamine‐dependent flare in vivo, but does not activate human skin mast cells in vitro.

“…We have previously reported that intradermal injection of endothelin-1 into the human forearm induces a vasoconstrictor response at the site of injection and a surrounding axon-reflex flare due to increased cutaneous blood flow (Brain et at., 1989;Crossman et at., 1991 (Benyon et al, 1987;El Lati et al, 1991;Lowman et al, 1988). However, platelet activating factor (PAF), which also causes an H1-receptor antagonist sensitive flare (Archer et al, 1985), does not release histamine from skin mast cells in vitro (Thomas & Church, 1990) suggesting that PAF stimulates mast cells by an indirect mechanism in vivo.…”

Datura stramonium Agglutinin Released Histamine from Rat Peritoneal Mast Cells That Was Inhibited by Pertussis Toxin, Haptenic Sugar and N-Acetylglucosamine-Specific Lectins: Involvement of Glycoproteins with A-Acetylglucosamine Residues

“…Rat peritoneal mast cells are a model system for the study of human skin mast cells as both cells respond to both IgE receptor-dependent and non-immunologic stimuli (7). The mast cell line RBL-2H3 is a model with which to study IgE-dependent signal transduction.…”