Characterization of neuropeptide-induced histamine release from human dispersed skin mast cells.
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 microM to 30 microM). 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-L-lysine, is rapid, reaching completion in 10-20 s, is largely independent of extracellular calcium but requires intact glycolysis and oxidative phosphorylation. 5. The substance P analogue, [D-Pro4,D-Trp7,9,10] SP4-11 (SPA), not only reduced substance P-induced 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 activation-secretion 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.
Lowman
M A
MA
Immunopharmacology Group, Southampton General Hospital.
Benyon
R C
RC
Church
M K
MK
D000255:Adenosine Triphosphate / Q000378:metabolism; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism; D000963:Antimetabolites / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide; D002118:Calcium / Q000502:physiology; D004600:Eledoisin / Q000037:antagonists & inhibitors; D004734:Energy Metabolism / Q000187:drug effects; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011961:Receptors, Fc / Q000378:metabolism; D017455:Receptors, IgE; D012867:Skin / Q000166:cytology; D013373:Substance P / Q000037:antagonists & inhibitors; D014660:Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors
D000944:Antigens, Differentiation, B-Lymphocyte; D000963:Antimetabolites; D009479:Neuropeptides; D011961:Receptors, Fc; D017455:Receptors, IgE; D013373:Substance P; D014660:Vasoactive Intestinal Peptide; D004600:Eledoisin; D000255:Adenosine Triphosphate; D015740:Calcitonin Gene-Related Peptide; D002118:Calcium