Substance P, calcitonin gene-related peptide, and capsaicin release serotonin from cerebrovascular mast cells

Rabbit leptomeningeal arteries contain granular cells resembling mast cells that frequently contact autonomic and sensory nerve profiles. In the present in vitro study, we determined whether these cells could be stimulated by substance P (SP) and calcitonin gene-related peptide (CGRP), which are stored and released by sensory C fibers. Immunohistochemistry of the middle cerebral artery showed that 5-HT was stored only in mast cell-like granules. This pool of 5-HT decreased in a dose-dependent manner when exogenous SP and CGRP were added to the incubation solution or when endogenous neuropeptides were released from nerve terminals by capsaicin. The simultaneous administration of CGRP and SP induced a dramatic exocytosis and a 5-HT release significantly greater than the sum of the individual effects of the two neuropeptides. We conclude that, as in classical connective tissue mast cells, the amine content of these granular cells can be released by a degranulation process induced by neuropeptides. The effects of capsaicin suggest that this phenomenon can be triggered by axon reflex of C fibers. The data also provide the first evidence of a synergistic action of SP and CGRP on mast cell degranulation.

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Release of Histamine from Dural Mast Cells by Substance P and Calcitonin Gene-Related Peptide

Cephalalgia ◽

10.1046/j.1468-2982.1997.1703166.x ◽

1997 ◽

Vol 17 (3) ◽

pp. 166-174 ◽

Cited By ~ 133

Author(s):

A Ottosson ◽

L Edvinsson

Keyword(s):

Mast Cells ◽

Substance P ◽

Histamine Release ◽

Dura Mater ◽

Neurogenic Inflammation ◽

Calcitonin Gene Related Peptide ◽

Sampling Procedure ◽

Related Peptide ◽

Calcitonin Gene ◽

Peritoneal Mast Cells

The aim of the present study was to examine if the neuropeptides substance P (SP), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP) can stimulate histamine release from mast cells in the dura mater and thereby play a role in cranial vasoregulation and local neurogenic inflammation. Dura mater mast cells were compared with peritoneal mast cells in the rat. Histamine was released from dura mater mast cells by compound 48/80, SP and CGRP but from peritoneal mast cells only by compound 8/80 and SP. NPY and VIP released quite small amounts of histamine from dural mast cells. The release on SP and CGRP from rat dura mater mast cells was blocked by the receptor antagonists FK888 and CGRP8-37 respectively, suggesting receptor mediated release mechanisms. None of the stimuli released histamine from human or porcine dural mast cells, possibly because the sampling procedure injures and incapacitates the cells.

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Substance P and calcitonin gene related peptide induce TGF-alpha expression in epithelial cells via mast cells and fibroblasts

Regulatory Peptides ◽

10.1016/j.regpep.2009.12.016 ◽

2010 ◽

Vol 161 (1-3) ◽

pp. 33-37 ◽

Cited By ~ 6

Author(s):

Peter Hoffmann ◽

Karoline Hoeck ◽

Susanne Deters ◽

Ilka Werner-Martini ◽

Wolfgang E. Schmidt

Keyword(s):

Mast Cells ◽

Substance P ◽

Epithelial Cells ◽

Calcitonin Gene Related Peptide ◽

Related Peptide ◽

Calcitonin Gene

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Trigeminal fibre collaterals storing substance P and calcitonin gene-related peptide associate with ganglion cells containing choline acetyltransferase and vasoactive intestinal polypeptide in the sphenopalatine ganglion of the rat. An axon reflex modulating parasympathetic ganglionic activity?

Neuroscience ◽

10.1016/0306-4522(89)90154-1 ◽

1989 ◽

Vol 30 (3) ◽

pp. 595-604 ◽

Cited By ~ 51

Author(s):

N. Suzuki ◽

J.E. Hardebo ◽

Ch. Owman

Keyword(s):

Substance P ◽

Vasoactive Intestinal Polypeptide ◽

Choline Acetyltransferase ◽

Ganglion Cells ◽

Calcitonin Gene Related Peptide ◽

Sphenopalatine Ganglion ◽

Axon Reflex ◽

Related Peptide ◽

Calcitonin Gene ◽

Intestinal Polypeptide

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Pharmacological evidence that calcitonin gene-related peptide is implicated in cerebral autoregulation

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1994.266.1.h11 ◽

1994 ◽

Vol 266 (1) ◽

pp. H11-H16 ◽

Cited By ~ 7

Author(s):

K. W. Hong ◽

K. M. Pyo ◽

W. S. Lee ◽

S. S. Yu ◽

B. Y. Rhim

Keyword(s):

Blood Pressure ◽

Substance P ◽

Calcitonin Gene Related Peptide ◽

K Channel ◽

Dependent Manner ◽

Receptor Desensitization ◽

Arterial Diameter ◽

Cranial Window ◽

Related Peptide ◽

Calcitonin Gene

In anesthetized rats, we examined the possibility that calcitonin gene-related peptide (CGRP, a neuropeptide) released in response to transient hypotension may contribute to the reflex autoregulation of cerebral blood flow. Changes in pial arterial diameter (mean 33.0 +/- 1.1 microns) with changes in systemic arterial blood pressure (mean 101.9 +/- 2.7 mmHg) were observed directly through a closed cranial window. In capsaicin-treated rats (depletor of CGRP and substance P, 50 nmol capsaicin injected intracisternally 24 h before experiment), vasodilatation, which was evoked on transient hypotension, and vasoconstriction on reverse of hypotension were markedly attenuated or almost abolished. When changes in pial arterial diameter were plotted as a function of changes in blood pressure, the slopes of regression lines for vasodilatation and vasoconstriction were markedly reduced after capsaicin treatment. Similar reductions were evidenced under suffusion of CGRP antibody serum (1:1,000) and after CGRP receptor desensitization but not after substance P receptor desensitization. Pretreatment with glibenclamide, a K(+)-channel antagonist, also caused severe alterations in the autoregulatory vasomotor responses to hypotension and its reverse. Suffusion with mock cerebrospinal fluid, containing either CGRP or cromakalim, a K(+)-channel opener, dilated the pial artery in a concentration-dependent manner, and their effects were antagonized by glibenclamide. Substance P produced a vasodilatation, which was unaffected by glibenclamide.(ABSTRACT TRUNCATED AT 250 WORDS)

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Substance P and Calcitonin Gene-Related Peptide: Effects on Mast Cells and in Human Skin

International Archives of Allergy and Immunology ◽

10.1159/000234229 ◽

1987 ◽

Vol 82 (3-4) ◽

pp. 366-371 ◽

Cited By ~ 112

Author(s):

J.C. Foreman

Keyword(s):

Mast Cells ◽

Substance P ◽

Human Skin ◽

Calcitonin Gene Related Peptide ◽

Related Peptide ◽

Calcitonin Gene

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Similar Distribution of Mast Cells and Substance P- and Calcitonin Gene-Related Peptide-Immunoreactive Nerve Fibers in the Adult Human Larynx

Annals of Otology Rhinology & Laryngology ◽

10.1177/000348949610501011 ◽

1996 ◽

Vol 105 (10) ◽

pp. 825-831 ◽

Cited By ~ 18

Author(s):

Siw Domeu ◽

Anders Eriksson ◽

Åke Dahlqvist ◽

Store Forsgren

Keyword(s):

Mast Cells ◽

Substance P ◽

Calcitonin Gene Related Peptide ◽

Nerve Fibers ◽

The Body ◽

Similar Distribution ◽

Related Peptide ◽

Adult Human ◽

Calcitonin Gene ◽

Human Larynx

The mechanisms causing supraglottic and subglottic edema in the human larynx are not fully understood. Substance P (SP)- and calcitonin gene-related peptide (CGRP)-containing nerve fibers and mast cells have been suggested to induce inflammation and edema in other parts of the body. In this study of the adult human larynx the distribution of mast cells was studied in relation to SP- and CGRP-containing nerve fibers. Substance P- and CGRP-immunoreactive nerve fibers and numerous mast cells were found in the epiglottis and in the subglottic region of the larynx. Only occasional mast cells and no nerve fibers showing SP- or CGRP-like irnmunoreactivity were found in the vocal cords. In conclusion, the present study has shown that the distribution of nerve fibers showing SP- and CGRP-like irnmunoreactivity and mast cells has a similar regional variability. As the highest density of SP- and CGRP-containing nerve fibers and mast cells was present in the regions of the larynx where edema occurs, SP, CGRP, and/or mast cells might be involved in the pathogenesis of edema.

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