Histaminic activity

Hardie, R. C. (1989). A histamine-activated chloride channel involved in neurotransmission at a photoreceptor synapse. Nature 339, 704-6. 

Histamine is stored within and released from neurons but a neuronal transporter for histamine has not been found. Newly synthesized neuronal histamine is transported into TM neuronal vesicles by the vesicular monoamine transporter VMAT2 [16]. Both in vivo and in vitro studies show that depolarization of nerve terminals activates the exocytotic release of histamine by a voltage- and calcium-dependent mechanism. Once released, histamine activates both postsynaptic and presynaptic receptors. Unlike the nerve terminals from other amine transmitters, however, histaminergic nerve terminals do not exhibit a high-affinity uptake system for histamine [5, 9, 23]. Astrocytes may contain a histamine transport system. 

Green, J. P., Johnson, C. L., Weinstein, H., and Maayani, S. (1977) Antagonism of histamine-activated adenylate cyclase in brain by D-lyseigic acid diethylamide. Proc. Natl. Acad. Sci. USA, 74 5697-5701. 

Histamine actively participates in functions and activity of DC precursors as well as their immature and mature forms. Immature and mature DCs express all four HRs [179-182]. In the differentiation process of type 1 DC from monocytes, HRl and HR3 act as positive stimulants that increase antigen-presentation capacity and proinflammatory cytokine production and Thl-priming activity. In contrast, HR2 acts as a suppressive molecule for antigen-presentation capacity, enhances IL-10 production and induces of IL-lO-producing T cells [183-185]. 

Animals exposed vivo to cotton dust show similar results. In excised tissues, histamine methylating enzymes fall to zero during exposure, but rise following a rest from cotton dust inhalation. In flax dust exposed animals, histamine activity initially increases.In guinea pigs, enzyme levels fall upon exposure, then rise after removal from exposure. Further, while flax exposed animals show a fall in total lung histamine content, with cotton dust exposure there is an increase. It should, however, be borne in mind that histamine release is not necessarily correlated with total lung histamine (103). 

TABLE 13.9. Medications that Reduce Histamine Activity... 

Medication Means of Reducing Histamine Activity Prominent Effects on Other Transmitters Psychiatric Uses... 

Seifert R, Hageluken A, Hoer A, Hoer D, Grunbaum L, Offermanns S, Schwaner I, Zinge V, Schunack W, Schultz G (1994) The HI receptor agonist 2-(3-chlorophenyl) histamine activates Gi proteins in HL-60 cells through a mechanism that is independent of known histamine receptor subtypes. Mol Pharmacol... 

In humans, injection or infusion of histamine causes a decrease in systolic and diastolic blood pressure and an increase in heart rate. The blood pressure changes are caused by the direct vasodilator action of histamine on arterioles and precapillary sphincters the increase in heart rate involves both stimulatory actions of histamine on the heart and a reflex tachycardia. Flushing, a sense of warmth, and headache may also occur during histamine administration, consistent with the vasodilation. Vasodilation elicited by small doses of histamine is caused by H -receptor activation and is mediated primarily by release of nitric oxide from the endothelium (see Chapter 19). The decrease in blood pressure is usually accompanied by a reflex tachycardia. Higher doses of histamine activate the H2-mediated cAMP process of vasodilation and direct cardiac stimulation. In humans, the cardiovascular effects of small doses of histamine can usually be antagonized by Hi-receptor antagonists alone. 

Occupied receptors for adrenaline, glucagon, ACTH, and histamine activate adenylate cyclase via Gs proteins. Other Gs proteins, which contain subunits designated aolf and which exist as a number of subtypes, mediate olfactory responses. Subunit aD is another specialized polypeptide which is located primarily in neural tissues. A variety of additional G proteins have been discovered in organisms ranging from bacteria to mammals.179 183-186 All have similar structures with 39- to 45-kDa a subunits, 35- to 36-kDa (3 subunits and 5- to 8-kDa y subunits. Whereas the a subunits are unique to each G protein, (3 and y subunits may be shared among several G proteins. These proteins appear to function with many kinds of hormone receptors and... 

Cafieri F, Camuccio R, Fattorusso E, Taglialatela-Scafati O, Vallefuoco T (1997) Anti-Histaminic Activity of Bromopyrrole Alkaloids Isolated from Caribbean Agelas Sponges. Bioorg Med Chem Lett 7 2283... 

Agrawal et al. have studied the anti-histaminic activity of these 2,3-disubstituted thiazolidin-4-one analogues (Table 9) with graph theoretical indices and discovered the following equation for the activity in terms of the rooted Wiener index (Ww), rooted Szeged index (Szw), molecular redundancy index (MRI), and an indicator variable Ipi (for the p-alkyl of the aryl... 

Table 9 Physicochemical properties and anti-histaminic activity of 2,3-disubstituted thiazolidin-4-ones derivatives (Fig. 10) [109]...

Table 10 Thiazole and benzthiazole derivatives in modeling the anti-histaminic activity (Fig. 11) [111,112] ...

Takizawa, H., Ohtoshi, T., Kikutani, T., Okazaki, H., Akiyama, N., Sato, M., Shoji, S., and Ito, K. (1995). Histamine activates bronchial epithelial cells to release inflammatory cytokines in vitro. Int. Arch. Allergy Immunol. 108, 260-267. 

Janssen, L.J. and Sims, S.M. (1993) Histamine activates O and K currents in guinea-pig tracheal myocytes convergence with muscarinic signalling pathway. Journal of Physiology (London), 465 661-677. 

As stated earlier, histamine activates two types of receptors viz., Hj and Hj receptors. The activation of H2 receptors leads to increased gastric acid secretion, increased contraction of the isolated atria and inhibition of isolated uterus. These effects are blocked by Hj-receptor antagonists which are now being used for the treatment of peptic ulcer. 

Cafieri, F., Camuccio, R., Fattorusso, E., Taglialatela-Seafati, O., Vallefuoco, T., (1997). Anti-histaminic activity of bromopyrrole alkaloids isolated from Caribbean Agelas sponges. Bioorg. Med. Chem. Lett. 7,2283-2288. 

With the recognition that a Cu complex of histamine was responsible for its histaminic activity. Walker and Reeves [116] suggested that a competition for this Cu accounted for the well-known observation that salicylic acid has antihistamine activity. They then demonstrated that salicylic acid prevented lethality in mice given an LDso dose of histamine. Since an increase in vascular permeability is an important physiological response in inflamed tissues, these observations merit in-depth study. 

Recent pharmacological and biochemical studies have provided evidence for five plausible Cu-dependent mechanisms of action which may account for the observed biologic activity of Cu complexes. These are induction of lysyl oxidase or lysyl oxidase mimetic activity, induction of superoxide dismutase or superoxide dismutase mimetic activity, modulation of prostaglandin synthesis, modulation of histamine activity, and lysosomal membrane stabilization. Ongoing research may provide evidence for still other Cu-dependent processes which may more fully explain the biologic activity of Cu complexes. 

Zymosan-bound histamine activated Oj formation in guinea pig alveolar macrophages via HI receptors (Diaz et al. 1979). 

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]. 

Caraway is generally considered to have carminative and stomachic properties. Caraway oil has been reported to exhibit antibacterial activities in vitro as well as larvicidal proper-ties. ° It also has antispasmodic and anti-histaminic activities on isolated animal organs (HANGSU). - ... 

Syntheses of tryptic peptides corresponding to the sequences 1—5 (11) and 69—73 (12) of hen egg-white lysozyme and to the sequence 1—5 (13) of turkey egg-white lysozyme have been described. The anti-histaminic activity of (11)—(13) was examined. 

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