H-2 receptors

Second-Generation Receptor Antagonists. Because of undesirable side effects caused by classical H receptor antagonists, dmgs... 

Hj Antihistamine Treatment in Allergic Diseases. H -receptor antagonists are used for the symptomatic treatment of several allergic... 

Atopic Dermatitis. The mechanism of itching associated with atopic dermatitis remains unknown, but histamine is almost certainly involved to some extent as histamine concentrations are increased in the skin and in the plasma of patients with this disorder (39,42). Second-generation H receptor antagonists, unlike first-generation H receptor antagonists, have not been uniformly found to be effective in relieving itching in atopic dermatitis, which may be related to the absence of a sedative effect (43). 

Antazoline H,-receptor antagonist Available only in combination with naphazoline... 

Levocabastine H,-receptor antagonist Downregulates intracellular adhesion molecules, decreasing the inflammatory response may be used for up to 2 weeks... 

Emedastine H,-receptor antagonist inhibits eosinophil chemotaxis Superior Hrreceptor binding ability... 

H2 receptors are associated with adenylate cyclase, and stimulation of these receptors increases the cytosolic concentration of cAMP and activation of cAMP-dependent protein kinase. Although inhibition of adenylate cyclase has been suggested as the intracellular signaling mechanism associated with H receptors, this has not been completely substantiated. 

Histamine acts on four G-protein-coupled receptors, three of which are clearly important in the brain 256 H, receptors are intronless GPCRs linked to Gq and calcium mobilization 256... 

H linked intracellular messengers. Activated H receptors are known to activate a pertussis-toxin-insensitive G protein, Gq, that stimulates phosphoinositide-specific phospholipase C (PI-PLC), with the subsequent generation of inositol 1,4,5-trisphosphate (IP3) and diacylglyc-erol (DAG). These two mediators are known to elevate intracellular Ca2+ concentrations and to activate PKC,... 

H, receptors also can stimulate the activity of phospholipase A2 (PLA2), with the subsequent release of arachido-nate and its metabolites. In platelets, this response does not require activation of the phosphoinositide cycle and is inhibited by pertussis toxin, suggesting a second, distinct Gj/o-protein-mediated transduction mechanism. In cells transfected with the H, receptor, PLA2 activation is partially inhibited by pertussis toxin, also suggesting at least two transduction systems [30,34],... 

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). 

Activation of brain H receptors also stimulates cGMP synthesis [19]. Outside the brain, histamine is known to relax vascular smooth muscle by activation of endothelial H receptors, thereby increasing endothelial Ca2+ concentrations and stimulating the synthesis and release of nitric oxide. The latter, a diffusible agent, then activates the smooth muscle guanylyl cyclase [30]. Although less is known about these mechanisms in the CNS, there is evidence that brain H receptor activation can produce effects that depend on guanylyl cyclase activity [19]. 

H receptor activation induces depolarizing responses in many brain areas, notably hypothalamus, thalamus and cerebral cortex. In vertebrate brain, many of these effects are mediated by opening cation channels. H,-induced excitation can also occur by blockade of KUak conductances [ 1 ]. In other cases, however, H, receptors can attenuate neuronal excitation by activating certain voltagegated potassium channels. Most of the H, receptor-induced conductance changes are mediated by the IP3-Ca2+ cascade. 

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