Release of vasoactive intestinal polypeptide in mast cells by histamine liberators

Wheal and flare reactions are described following intradermal injections of somatostatin, vasoactive intestinal polypeptide, substance P and histamine in normal human forearm skin. Bombesin failed to produce a significant wheal and flare. Pretreatment of skin with capsaicin in all cases dramatically inhibited the flare but not the wheal. This result is in accord with the hypothesis that capsaicin blocks the effector side of the axon reflex, perhaps by depleting nerve terminals of vasodilatory peptide(s).

Section: Discussionsupporting

confidence: 78%

Topical capsaicin pretreatment inhibits axon reflex vasodilatation caused by somatostatin and vasoactive intestinal polypeptide in human skin

Anand

Bloom

McGregor

1983

“…Since it stimulates the proliferation of keratinocytes, it has been speculated that VIP, released from sensory nerve endings in the skin, may be involved in wound healing (Haegerstrand et al, 1989). Another rich source of VIP is mast cells (Cutz et al, 1978) which are frequently localized around blood vessels in tissues and VIP released from these cells is likely to promote wound healing. Also, angiogenesis is a hallmark of inflammation, it is especially important in both the healing process which follows an acute inflammatory response and in chronic inflammatory diseases.…”

Section: Discussionmentioning

confidence: 99%

Comparative studies of the angiogenic activity of vasoactive intestinal peptide, endothelins‐1 and −3 and angiotensin II in a rat sponge model

Hiley

Fan

1996

The angiogenic activity of four vasoactive peptides with a range of vasodilator and vasoconstrictor properties, i.e. vasoactive intestinal peptide (VIP), endothelin‐1, endothelin‐3 and angiotensin II, were investigated in a rat sponge model. Neovascularization was assessed by the 133Xe clearance technique and confirmed by histological studies. Daily doses of the vasodilator peptide, VIP (1000 pmol), caused intense neovascularization, but a lower dose (10 pmol) produced no apparent effect. However, the lower dose of VIP, when given with a subthreshold dose of interleukin‐1α (0.3 pmol), produced an angiogenic response similar to that seen with the higher dose of VIP. The neovascular response induced by co‐administration of VIP and interleukin‐1α was inhibited by simultaneous administration of 100 pmol VIP (10–28), a specific VIP receptor antagonist. In contrast, daily doses of 10, 100 or 1000 pmol endothelin‐3 (a mixed vasoconstrictor and vasodilator with more marked vasodilator activity) or of 100 or 1000 pmol endothelin‐1 (also with mixed activity but with much more pronounced vasoconstrictor response) produced no apparent effect on sponge‐induced angiogenesis. The vasoconstrictor peptide, angiotensin II, in daily doses of 1000 pmol, caused an intense neovascularization like VIP but lower doses of angiotensin II (10 or 100 pmol) produced no apparent effect. The lowest dose of angiotensin II (10 pmol) when administered with the subthreshold dose of interleukin‐1α (0.3 pmol) had no effect on the basal neovascular response in the sponges. The angiotensin II‐induced neovascular response was inhibited by co‐administration of 100 nmol of the specific AT1 receptor antagonist, losartan, but not by the AT2 receptor antagonist, PD 123319. These data show that VIP and angiotensin II possess angiogenic activity. However, endothelin‐1 and endothelin‐3 had no activity at the doses used. Thus the angiogenic response is not related to local vasoconstriction or vasodilatation in the sponges. The blockade of VIP‐ and angiotensin II‐induced angiogenesis at the receptor level suggests that receptor modulation could provide a strategy for the management of angiogenic diseases.

“…A role for neuropeptides in both negative and positive feedback mechanisms regulating mediator release from immune cells is suggested by the presence of somatostatin-like peptides in rat basophilic leukaemia (RBL) cells (Goetzl et al, 1985) and VIP immunoreactivity in rat peritoneal mast cells (Cutz et al, 1978). Somatostatin-like peptides from RBL cells appear to inhibit mediator release from these cells whereas VIP immunoreactivity, which is released from rat peritoneal mast cells in response to compound 48/80, may stimulate further mast cell mediator release.…”

Section: Discussionmentioning

confidence: 99%

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

Lowman

Benyon

Church

1988

199

103

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.