Inhibition histamine release

The Hi Receptor and its Ligands. The H receptor mediates effects, through an increase in cyclic adenosine monophosphate (cAMP). such as gastric acid secretion relaxation of airway smooth muscle and of pulmonary vessels increased lower airway mucus secretion esophageal contraclion inhibition of basophil, but not mas cell histamine release inhibition of neutrophil activation and induction or suppressor T cells. There is no evidence that the H- receptor causes significant modulation of lung function in the healthy human subject or in the asthmatic. 

Aromoline and ten other bisbenzylisoquinoline alkaloids were evaluated in the in vitro histamine release inhibition assay. This assay is one of the basic tests that is used in the evaluation of substances for antiallergic effects. The order of potency of inhibitory effect of those bisbenzylisoquinoline alkaloids that have been isolated from Thalictrum species was as follows homoaromoline > aromoline > isotetrandrine > obaberine > tetrandrine. Berbamine and oxyacanthine were found to have no inhibitory effect [178]. 

The synthesis of a series of triazolobenzopyranones carrying piperazinoalkoxy substituents on the phenyl ring demonstrated the feasibility of integrating the mast-cell-stabilizing properties of the chromone (benzopyranone) moiety and H( antihistaminic properties into one molecule. The most effective compound of a small series was BR-28390. Its antihistaminic potency (guinea pig ileum) was the same as mepyramine histamine release inhibition effectiveness (tested by rat passive peritoneal anaphylaxis) was somewhat less than cromolyn. 

Concentration of compound pg/ml Net histamine release % Inhibition % Concentration of compound pg/ml Net hi stami ne release % Inhibition %... 

Apoptosis induction Protein kinase C inhibition Histamine release inhibition Modulation of cell cycle... 

Histamine release inhibition - in vitro (rat, sarcolema-black) at 0.1 mM. Assay done on given cells after passive... 

Attaching some short peptidic sequences to adamantane makes it possible to design novel antagonists. The bradykinin antagonist, which is used as an anticancer agent, is an example. The adamantane-based peptidic bradykinin analog was utilized in strucmre-activity relationship (SAR) studies on the bradykinin receptors and showed a potent activity in inhibition of bradykinin-induced cytokine release and stimulation of histamine release [142]. 

Hj antihistamines are the most commonly prescribed medications for AR. Hj antihistamines bind to and stabilize the Hj histamine receptor, thereby inhibiting mast cell and basophil mediator release and resulting in reduction of sneezing, itching, rhinorrhea, and ocular irritation. Antihistamines do not prevent histamine release, nor do they bind to already-released histamine. For this reason, maintenance therapy is considered optimal. However, antihistamines are also effective when taken on an as-needed basis.4,11,12 Antihistamines only minimally... 

He SH, Xie H, Zhang XJ, Wang XJ. Inhibition of histamine release from human mast cells by natural chymase inhibitors. Acta Pharmacol Sin. 2004 25 822-826. 

Arrang, J. M., Garbarg, M. Schwartz, J. C. (1983). Auto-inhibition of brain histamine release mediated by a novel class (H3) of histamine receptor. Nature 302, 832-7. 

We recently demonstrated that CGS21680, an adenosine A2aR agonist, inhibited histamine release in both the frontal cortex and medial POA in a dose-dependent manner, and increased GABA release specifically in the TMN but not... 

Histamine also induces antinociceptive (i.e. pain-relieving) responses in animals after microinjection into several brain regions [73, 74]. H, and H2 mechanisms are significant and both neuronal and humoral mechanisms may be involved. Brain H2 receptors appear to mediate some forms of endogenous analgesic responses, especially those elicited by exposure to stressors [75]. Many of the modulatory actions of histamine discussed above appear to be activated as part of stress responses. For reasons that remain unclear, histamine releasers, such as thioperamide, show only mild, biphasic antinociceptive actions, even though histamine is a potent and effective analgesic substance. Outside the brain, both H and H3 receptors exist on certain types of sensory nerves and activation of these receptors promotes and inhibits, respectively, peripheral nerve transmission related to pain and/or inflammation [76,77]. 

The ability of SP to stimulate histamine release from isolated rat peritoneal mast cells is now well demonstrated [31, 97-101], The release is rapid (< 1 min), non-cytotoxic, dependent on a supply of Ca and metabolic energy, and independent of cell-bound IgE [99]. Moreover, as with other peptides, its secretory effect on the mast cell is affected by moderate levels of extracellular cations. For example, the addition of Ca to the bathing medium after the addition of SP increased the secretory response of the cells, while adding calcium (0.1-1 mM), magnesium (1-10 mM) or cobalt (0.01-1 mM) to the cell suspension before SP inhibited histamine release, suggesting the possibility of cation competition for SP binding [99]. 

Acid acetone extracts of human and rodent leukocytes (RBL-cells) have been found to contain immunoreactive SOM (iSOM) and immunoreactive SP (iSP) as determined by radioimmunoassay [144], Quantities of the peptides varied from 325 pg iSOM/107 cells for human monocytes and 272 pg iSOM/107 cells for RBL-cells to 4.4 pg iSOM/107 cells for human T cells. iSP was highest in murine bone marrow-derived mast cells (64 pg iSP/107 cells) and RBL-cells (23 pg iSP/107 cells) and lowest in human T and B lymphocytes (2.5 and 1.2 pg iSP/107 cells, respectively). Interestingly, the murine bone marrow-derived mast cells had the highest ratio of iSP to iSOM. Preliminary chromatographic results show a large and a small SOM (SOM-28 and SOM-14, respectively). SOM-14 (3 x 10 9 M) has been shown to inhibit histamine release and LTC4 generation from murine bone marrow-derived mast cells stimulated by anti-IgE serum [144]. 

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