Histamine-like activity

Figure 6.1 Histamine synthesis and metabolism in neurons. L-histidine is transported into neurons by the L-amino acid transporter. Once inside the neuron, L-histidine is converted into histamine by the specific enzyme histidine decarboxylase. Subsequently, histamine is taken up into vesicles by the vesicular monoamine transporter and stored there until released. In the absence of a high-affinity uptake mechanism in the brain, released histamine is rapidly degraded by histamine methyltransferase, which is located postsynaptically and in glia, to telemethylhistamine, a metabolite that does not show any histamine-like activity.

Code CF, MacDonald AD. The histamine-like activity of blood. Lancet 2 730-733, 1937 Code CF. The histamine-like activity of white blood cells. J Physiol Lond 485-500, 1937. 

In monocytes stimulated with Toll-like receptor-triggering bacterial products, histamine inhibits the production of proinflammatory IL-1-like activity, TNF-a, IL-12 and IL-18, but enhances IL-10 secretion, through HR2 stimulation [26, 69]. Histamine also downregulates CD 14 expression via Hj receptors on human monocytes [70]. The inhibitory effect of histamine via Hj receptor appears through the regulation of ICAM-1 and B7.1 expression, leading to the reduction of innate immune response stimulated by LPS [71]. 

Synthetic compounds, pentazocine and Darvon, which have morphine-like activity, and their effects on the pituitary-adrenocortical system. Morphine-like inhibitory effect on histamine ACTH-releasing action... 

Several other substances which have hormone-like activity are widely distributed and exert their effects in the area in which they are produced. Histamine, serotonin and various plasma kinins may be considered to be local hormones. 

Since lysyl oxidase, the enzyme responsible for tissue repair, is copper-dependent, the possibility exists that lysyl oxidase activity could be induced by copper. The SOD-like activity of many active copper complexes, and the antiinflammatory effects of SOD itself, offer another possibility. Modulation of prostaglandin synthesis by Cu salts [96, 97] stabilization of lysosomal membrane by membrane thiol oxidation [98], stabilization of globulin [89], and alteration of histaminic activity and T-lymphocyte responses have been invoked [64]. 

The chemopreventive activity of hibiscus extracts has been extensively studied recently. The protective effect was demonstrated against human carcinomas, chemically induced toxicity,and hepatotoxici-jy 11,21-27 Antimutagenic activity has also been demonstrated both in vitro and in vivo The chemopreventive activity is attributed mainly to the antioxidant effect of the anthocyanins present in hibiscus extracts. Roselle decoction or infusion reportedly has hypotensive properties with no side effects. This effect has been investigated in more depth in experimental animals and in humans over the past decade and the results seem to support earlier studies especially in mild to moderate hypertension. Suggested mechanisms of action for the hypotensive activity include inhibition of Ca influx into vascular smooth muscle, NO-cGMP-relaxant pathway, and possible acetylcholine-and histamine-like vasorelaxation. ... 

Melatonin [73-31-4] C 2H N202 (31) has marked effects on circadian rhythm (11). Novel ligands for melatonin receptors such as (32) (12), C2yH2gN202, have affinities in the range of 10 Af, and have potential use as therapeutic agents in the treatment of the sleep disorders associated with jet lag. Such agents may also be usehil in the treatment of seasonal affective disorder (SAD), the depression associated with the winter months. Histamine (see Histamine and histamine antagonists), adenosine (see Nucleic acids), and neuropeptides such as corticotropin-like intermediate lobe peptide (CLIP) and vasoactive intestinal polypeptide (VIP) have also been reported to have sedative—hypnotic activities (7). 

Important products derived from amino acids include heme, purines, pyrimidines, hormones, neurotransmitters, and biologically active peptides. In addition, many proteins contain amino acids that have been modified for a specific function such as binding calcium or as intermediates that serve to stabilize proteins—generally structural proteins—by subsequent covalent cross-hnk-ing. The amino acid residues in those proteins serve as precursors for these modified residues. Small peptides or peptide-like molecules not synthesized on ribosomes fulfill specific functions in cells. Histamine plays a central role in many allergic reactions. Neurotransmitters derived from amino acids include y-aminobutyrate, 5-hydroxytryptamine (serotonin), dopamine, norepinephrine, and epinephrine. Many drugs used to treat neurologic and psychiatric conditions affect the metabolism of these neurotransmitters. 

Histamine receptors were first divided into two subclasses Hi and H2 by Ash and Schild (1966) on the basis that the then known antihistamines did not inhibit histamine-induced gastric acid secretion. The justification for this subdivision was established some years later when Black (see Black et al. 1972) developed drugs, like cimetidine, that affected only the histamine stimulation of gastric acid secretion and had such a dramatic impact on the treatment of peptic ulcers. A recently developed H2 antagonist zolantidine is the first, however, to show significant brain penetration. A further H3 receptor has now been established. It is predominantly an autoreceptor on histamine nerves but is also found on the terminals of aminergic, cholinergic and peptide neurons. All three receptors are G-protein-coupled but little is known of the intracellular pathway linked to the H3 receptor and unlike Hi and H2 receptors it still remains to be cloned. Activation of Hi receptors stimulates IP3 formation while the H2 receptor is linked to activation of adenylate cyclase. 

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