Histamine regulation

Histamine contributes to the progression of allergic-inflammatory responses by enhancement of the secretion of proinflammatory cytokines like IL-la, IL-1(3, IL-6 as well as chemokines like RANTES or IL-8, both in several cell types and local tissues [26-29]. Endothelial cells express functional HRl and HR2 and increased adhesion molecule expression such as ICAM-1, VCAM-1 and P-selectin was demonstrated by histamine infusion via HRl [30-32]. Histamine regulates the expression of its own receptors on endothelial cells and influences the overall inflammatory reaction [33]. 

Histamine regulates granulocyte accumulation to tissues in distinct ways. Allergen-induced accumulation of eosinophils in the skin, nose and airways is potently inhibited by Hj antihistamines [34]. The effect of histamine on eosinophil migration may differ according to the dose. Whereas high doses inhibit eosinophil chemotaxis via... 

Mazzoni A, Young HA, Spitzer JH, Visintin A, Segal DM Histamine regulates cytokine production in maturing dendritic cells, resulting in altered T cell polarization. J Clin Invest 2001 108 1865-1873. 

Jutel M, Watanabe T, Klunker S, Akdis M, Thomet OAR, Malolepszy J, et al Histamine regulates T-cell and antibody responses by differential expression of H, and Hj receptors. Nature 2001 413 420-425. 

Like prostaglandins, histamine regulates numerous processes, including acid and pepsin secretion in the stomach, heart rate and vasodilation. Histamine antagonists which prevent acid and pepsin secretion are clinically used to treat peptic ulcer disease (Table 6.1). 

A role for histamine-regulated HDC activity in histamine secretion was initially postulated by Kahlson in 1964. Histamine secretion and synthesis are intimately coupled, and store depletion is often the signal for enzyme synthesis. HDC activation may be initiated by such an event. A second possibility is that... 

Because histamine in the CNS is important for the regulation of sleep/wakehilness, appHcations in this area could be found. In cats, the receptor has been shown to affect the sleep pattern, and it has also been impHcated in this respect in rats and mice (8). 

Certain amino acids and their derivatives, although not found in proteins, nonetheless are biochemically important. A few of the more notable examples are shown in Figure 4.5. y-Aminobutyric acid, or GABA, is produced by the decarboxylation of glutamic acid and is a potent neurotransmitter. Histamine, which is synthesized by decarboxylation of histidine, and serotonin, which is derived from tryptophan, similarly function as neurotransmitters and regulators. /3-Alanine is found in nature in the peptides carnosine and anserine and is a component of pantothenic acid (a vitamin), which is a part of coenzyme A. Epinephrine (also known as adrenaline), derived from tyrosine, is an important hormone. Penicillamine is a constituent of the penicillin antibiotics. Ornithine, betaine, homocysteine, and homoserine are important metabolic intermediates. Citrulline is the immediate precursor of arginine. 

Histamine is a biogenic amine that is widely distributed in the body and functions as a major mediator of inflammation and allergic reactions, as a physiological regulator of gastric acid secretion in the stomach, as a neurotransmitter in the central nervous system (CNS) and may also have a role in tissue growth and repair. 

Schaefer U, Schneider A, Rixen D, Neugebauer E (1998) Neutrophil adhesion to histamine stimulated cultured endothelial cells is primarily mediated via activation of phospholipase C and nitric oxide synthase isozymes. Inflamm Res 47(6) 256-264 Schaefer U, Schmitz V, Schneider A, Neugebauer E (1999) Histamine induced homologous and heterologous regulation of histamine receptor subtype mRNA expression in cultured endothelial ceUs. Shock 12(4) 309-315... 

Histamine Hi, Hj Hz G, Gs Phospholipase-C to IPzto [Ca +]i regulation Stimulates adenylyl cyclase raising cAMP... 

Morisset, S., Rouleau, A., Iigneau, X. el al. (2000). High constitutive activity of native H3 receptors regulates histamine neurons in brain. Nature 408, 860-4. 

Monti, J. M., Orellana, C., Boussard, M., Jantos, H. Olivera, S. (1990). Sleep variables are unaltered by zolantidine in rats are histamine H2-receptors not involved in sleep regulation Brain Res. Bull. 25, 229-31. 

Munakata, M. Akaike, N. (1994). Regulation of K+ conductance by histamine HI and H2 receptors in neurones dissociated from rat neostriatum. J. Physiol. 480, 233-45. 

Figure 13.2 Schematic representation of the molecular mechanisms of sleep wake regulation by PGD2, PGE2, adenosine, histamine, and orexin.

It has been well documented that the anaemia of chronic disease, ACD, results in a lowering of various haematological parameters. Several mediators are involved, among them histamine, serotonin, bradykinin, prostaglandins and, as found more recently, cytokines and nitric oxide. ACD is a parameter of systemic autoimmune disorders. The severe inflammatory stimuli lead to several systemic changes, mediated by inflammation-associated cytokines, e.g. IL-6, IL-1 TNFa, TGF beta that regulate hepatic synthesis of the acute phase proteins. 

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