Signaling Pathways

Author: Gianpiero Pescarmona
Date: 02/04/2008



Autacoids: histamine and bradykinin

Histamine synthesis

Histidine Decarboxylase Expression

Histamine Localization

Histamine-containing peripheral neuronal and endocrine systems. 1985

  • Abstract
    An immunohistochemical method was developed to detect histamine in tissues. The aim of this study was to reveal the cellular stores of histamine in the gastrointestinal tract, pituitary, and adrenal gland. Histamine-containing nerve fibers were found in both rat and guinea pig gut. The origin of at least some of these fibers in the rat ileum was the submucous ganglion cell layer. In the rat stomach, numerous enterochromaffin-like cells exhibited histamine immunofluorescence, and endocrine cells in the ileum and jejunum contained histamine. Only mast cells contained histamine in the neurohypophysis. A large number of process-bearing cells in the guinea pig but not in the rat adrenal medulla contained histamine. The study shows that histamine is present in peripheral nerves and endocrine cells in addition to mast cells, and may function as a neurotransmitter or hormone.

Histamine storage and release

Fluvastatin inhibits mast cell degranulation without changing the cytoplasmic Ca2+ level. 2009

The statin-induced inhibitory action may be mediated by the suppression of geranylgeranyl transferase via the depletion of intracellular mevalonic acid.

Histamine Targets

Histamine Receptors

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Gagnemo-Persson R, Persson P, Bryngelsson T, Green B, Hakanson R.

Rat stomach ECL-cell histidine decarboxylase activity is suppressed by ergocalciferol but unaffected by parathyroid hormone and calcitonin.
Regul Pept. 1999 Feb 5;79(2-3):131-9.
PMID: 10100926 [PubMed - indexed for MEDLINE]

Neuroscience. 2004;125(3):535-40.Click here to read Links
Hypothalamic neuronal histamine regulates sympathetic nerve activity and expression of uncoupling protein 1 mRNA in brown adipose tissue in rats.
Yasuda T, Masaki T, Sakata T, Yoshimatsu H.

Department of Internal Medicine I, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama, Oita 879-5593, Japan.

To clarify how hypothalamic neuronal histamine regulates peripheral energy expenditure, we investigated the effect of infusion of histamine into the third cerebral ventricle or discrete hypothalamic regions on sympathetic nerve activity and expression of uncoupling protein 1 (UCP1) mRNA in brown adipose tissue (BAT). Infusion of histamine (200 nmol) into the third cerebral ventricle of anesthetized rats significantly increased the electrophysiological activity of sympathetic nerves (P<0.01) and UCP1 mRNA expression in the BAT (P<0.05). Microinjection of histamine (10 nmol) into the paraventricular nucleus (PVN) and preoptic area (POA) produced similar significant increases in BAT sympathetic nerve activity (P<0.01 for each). By contrast, injection of histamine into the ventromedial hypothalamic nucleus or lateral hypothalamic area had no effect. We conclude that hypothalamic neuronal histamine may regulate energy expenditure in BAT through the activation of sympathetic nerves. The PVN and/or POA appear to be the principal hypothalamic sites that mediate the stimulatory effect of histamine on this efferent pathway.

Targeted disruption of H3 receptors results in changes in brain histamine tone leading to an obese phenotype. 2002

More on histamine..

VEGF, substance P and stress, new aspects: a revisited study. 2010 J Biol Regul Homeost Agents. 2010 Jul-Sep;24(3):229-37.
Castellani ML, Galzio RJ, Felaco P, Tripodi D, Toniato E, De Lutiis MA, Conti F, Fulcheri M, Conti C, Theoharides TC, Caraffa A, Antinolfi P, Felaco M, Tete S, Pandolfi F, Shaik-Dasthagirisaheb YB.

Mast cells play an essential role in diverse physiological and pathological processes, such as atherosclerosis, malignancy, asthma, pulmonary fibrosis and arthritis, directly interact with bacteria, and appear to play a vital role in host defense against pathogens. Mast cells could be recruited in the inflammatory site, by MCP-1, RANTES and SCF, to selectively secrete proinflammatory molecules; these could include growth factors, histamine, which is mitogenic (H1) and an immunosuppressant (H2), neovascularization agents, such as heparin, IL-8, and VEGF, as well as proteases that could permit new blood vessel formation. Neurogenic inflammation involves vasodilation and plasma protein extravasation in response to neural stimulation. Upon stimulation, sensory neurons release Substance P and other neuropeptides and activate neurokinin-1 receptors leading to plasma protein extravasation from post-capillary venules. Substance P is a neuropeptide that is released from nerve endings in many tissues and plays an important role in immunological and inflammatory states, and it is also a mediator of tissue injury, asthma, arthritis, allergy and autoimmune diseases. SP-positive nerve fibers and mast cell contacts are increased by acute stress in mice leading to dermal mast cell degranulation. VEGF is produced by flammatory cells. IL-33 is the newest inflammatory member of the IL-1 cytokine family and we show here that SP can induce VEGF secretion from mast cells and IL-33 augments the effect of SP in VEGF transcription and translation protein.

Histamine breakdown

Histamine - beyond mastcells


Your Favorite Gene Sigma"URL":

Protein Aminoacids Percentage (Width 700 px)


mRNA synthesis
protein synthesis

post-translational modifications


cellular localization,
biological function

  • Enzymes
BRENDA - The Comprehensive Enzyme Information System"URL":
KEGG PathwaysHistamine
Human Metabolome Database"URL":
  • Cell signaling and Ligand transport
  • Structural proteins


Cofactor for gaba, dopamine and histamine?

The pathway of histamine synthesis stimulation and inverse agonist through histidine decarboxylase (HDC). Up-regulation of H1-histamine receptor is induced by IL-4 through the activation of H1-histamine receptor genes and histidine decarboxylase gene. Antihistamines has a mechanism to inhibit the up-regulation of H1-histamine gene expression and suppress histamine basal signal through inverse agonistic activity. Downregulation of H1-histamine gene expression by antihistamines occurs through suppression of histidine decarboxylase and IL-4 gene transcription.


2012-05-17T20:50:46 - Gianpiero Pescarmona

Anxiety Histamine

The results suggest that histamine may modulate anxiety via H1 but not H2 receptors in the rat central amygdala.

2012-03-24T23:34:39 - Gianpiero Pescarmona

Histamine breakdown

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