Histamine receptors/effects

F. M. Cuss (1999). Beyond the histamine receptor effects of antihistamines on mast cells. Clin. 

Antihistamine. Compound that, by occupying the histamine receptors, antagonizes the effects of histamine. 

The term antihistamines describes drags which bind to the Hi-histamine receptor and antagonize (block) the histamine effect in Type I allergic responses. 

Several histamine receptor antagonists are effective in treating motion sickness, Meniere s disease, morning sickness, uraemia and postoperative vomiting. They are not effective against cytotoxics. Antagonists with... 

Antihistamines block most, but not all, of die effects of histamine They do this by competing for histamine at histamine receptor sites, diereby preventing histamine... 

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... 

The experiment of Figure 1.7 points to the same conclusion. When very low concentrations of histamine are applied in the presence of a relatively large fixed concentration of impromidine, the overall response is mainly due to the receptors occupied by impromidine however, the concentration-response curves cross as the histamine concentration is increased. This is because the presence of impromidine reduces receptor occupancy by histamine (at all concentrations) and vice versa. When the lines intersect, the effect of the reduction in impromidine occupancy by histamine is exactly offset by the contribution from the receptors occupied by histamine. Beyond this point, the presence of impromidine lowers the response to a given concentration of histamine. In effect, it acts as an antagonist. Again, the implication is that the partial agonist can combine with all the receptors but is less able to produce a response. 

It was noted, however, that a subset of responses known to be triggered by histamine failed to be blocked by the classical antihistaminic drugs. This, as well as further sophisticated pharmacological work, led to the classification of histamine receptors as and Hg. To simplify grossly, the receptor controls the responses familiar to every hayfever sufferer these effects can be alleviated readily by classicial antihistamines. The latter interestingly bear little or no structural similarity to histamine... 

Transmitter Transmitter parameter Receptor Effect Histamine parameter Receptor Effect... 

H, receptors in brain slices can also stimulate glycogen metabolism [5] and can positively modulate receptor-linked stimulation of cAMP synthesis. The activation of brain cAMP synthesis by histamine is a well studied phenomenon that reveals a positive interaction between histamine receptors [35]. When studied in cell-free preparations, this response shows characteristics of H2, but not H receptors. When similar experiments are performed in brain slices, however, both receptors appear to participate in the response. Subsequent work showed that H receptors do not directly stimulate adenylyl cyclase but enhance the H2 stimulation, probably through the effects of calcium and PKC activation on sensitive adenylyl cyclase iso forms (see Ch. 21). 

Neurotensin (NT) is a tridecapeptide (Table 4.2) first isolated from brain and gut by Carraway and Leeman [75] and reported by them to induce a rapid and transient hypotension, a cutaneous vasodilatation, and a cyanosis of the extremities in the anaesthetized rat. This report, along with others [76-78] indicating that the NT-induced hypotension and increased vascular permeability could be blocked by histamine receptor antagonists such as mepy-ramine [77] or by pretreatment with compound 48/80 [76], suggested that endogenous histamine (perhaps released from tissue mast cells) was involved in producing some of the biological effects of NT [78]. 

Regulatory Effects of Histamine and Histamine Receptor Expression in Human Allergic Immune Responses... 

Histamine receptor HI E349D, L449S, Many SNPs No association with atopic L449S probably no effect on (97,279-281) ... 

Histamine receptor H2 R649G, SNPs Some evidence for t fre- No effect on clozapine (280(282(283) o o... 

Medications that enhance norepinephrine activity are used to treat depression and ADHD. Boosting norepinephrine can also produce numerous side effects including nervousness and anxiety, insomnia, and loss of appetite. With mirtazapine and the TCAs, these side effects are usually not a problem because these antidepressants also block histamine receptors. Their antihistamine effects promote increased appetite and drowsiness that tend to offset the side effects that might be experienced from increased norepinephrine activity. 

Diphenhydramine is the antihistamine that is most widely used by psychiatrists, and it is most often used more for its acetylcholine-blocking effects than its histamine blockade. This is not to say that histamine-blocking effects are not problematic. In fact, a wide variety of psychiatric medications block histamine receptors. The... 

Blockade of histamine receptors. Allergic reactions are predominantly mediated by H receptors. Hi antihistamines (p. 114) are mostly used orally. Their therapeutic effect is often disappointing. Indications allergic rhinitis (hay fever). 

This lack of complete effectiveness led to the hypothesis that a second type of histamine receptor existed. In 1972, Black et al. (55) discovered a new series of antagonists which they called H2 receptor blockers. Burimamide was the first highly effective H2 blocker, but it was poorly absorbed orally. The modified compound, metiamide, had better absorption but was found to cause granulocytopenia (57.58). Finally, cimetidine was tested and found to be a potent and relatively non-toxic antagonist (59). Cimetidine is now widely used clinically to treat duodenal ulcers, Zollinger-Ellison Syndrome and other gastric hypersecretory diseases (32). 

Histamine also acts on extravascular smooth muscles to cause contraction or relaxation. Most often, contraction is due to activation of Hj receptors and relaxation to activation of H2 receptors (32). In man, histamine causes contraction of bronchial and intestinal smooth muscles. Histamine-induced contraction of guinea pig ileum is a standard bioassay for histamine. Its effects on smooth muscle of the eye and genitourinary tract are important in some species but not in human ( ). In scombroid poisoning cases. 

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