Histamine GPCRs

Agonists of GPCRs a, p Agonists, histamine, 5HT2c agonists, endothelin-1, angiotensin-ll... 

Most GPCRs interact with and activate more than one G-protein subfamily, e.g., with Gs plus Gq/n (histamine H2, parathyroid hormone and calcitonin recqrtors), Gs plus G (luteinising hormone receptor, 32-adrenoceptor) or Gq/11 plus G12/13 (thromboxane A2, angiotensin ATb endothelin ETA receptors). Some receptors show even broader G-protein coupling, e.g., to Gi, Gq/n plus Gi n ( protease-activated receptors, lysophosphatidate and sphingosine-1-phosphate receptors) or even to all four G-protein subfamilies (thyrotropin receptor). This multiple coupling results in multiple signaling via different pathways and in a concerted reaction of the cell to the stimulus. 

The authors also identified the most common structural motifs unique to ligands of individual classes of GPCRs such as the adrenergic, dopamine, histamine, muscarinic, and serotonin receptors as shown in Table 1. 

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... 

Antihistamines are antagonists of histamine receptors that displace histamine competitively from its receptors and block the effects of histamine. Histamine receptors, in turn, are G-protein-coupled receptors (GPCRs) that contain the typical seven-transmembrane loop motif. Other common GPCRs include calcium channel receptors, andrenergic ai, dopamine D2, serotonin 5-HT2 and muscarinic receptors. They have... 

Hamdan et al. (2002) describe another biogenic amine-responsive GPCR in the tegument of S. mansoni, which specifically binds to and is activated by histamine. This cloned receptor shares approximately 30% amino acid sequence homology with other major amine GPCRs, and, when transfected into mammalian cells exhibited the following characteristics ... 

The 5-HT6 receptor was first cloned by sequence homology with another GPCR receptor, the histamine H2 receptor, from a rat brain cDNA library (206) and by PCR from a rat striatal cDNA library (207). Later, the human (208) and the mouse (209) 5-HT6 receptors were also cloned. This receptor... 

Histamine receptors variously mediate the bronchoconstrictant, inflammatory, irritant, vasodilator, gastric pepsin secretion and immune suppression actions of histamine. Associated with the immune response, cytokines cause release of histamine from mast cells. Histamine acts via HI, H2, H3 and H4 GPCRs. HI and H2 receptors couple via both Gas (elevating cAMP) and Gaq (elevating Ca2+ in a pertussis toxin-insensitive fashion) and H3 couples via Gai (decreasing cAMP). 

The endogenous agonists and antagonists may be very large molecules, say a peptide that is in specific cases, 11, 30, 36, or 41 amino acids long, or as large as trombin protein that also activates a GPCR Just like the small molecules noradrenaline, histamine, and so on. 

Initial efforts to identify orphan receptors exploited PCR methodology to clone several novel orphan receptors belonging to the GPCR superfamily. These orphan receptors were subsequently shown to include the adenosine Ai and A2a receptors,a S-HTid receptor,and a central cannabinoid receptor (CBi). PCR using degenerate primers was subsequently used to identify cDNAs encoding the NKi, NK2, dopamine Dj and histamine H3,... 

Note that one endogenous mediator may activate several GPCRs 13 for serotonin 9 for adrenaline and noradrenaline 8 for glutamate 5 for dopamine 5 for acetylcholine 4 for histamine 2 for GABA. Also, some mediators activate GPCRs but also receptors with intrinsic ion channel. 

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