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Many of the histaminergic neurons lay in close proximity to the third ventricle or are located on the ventral surface of the brain, suggesting, like other hypothalamic neurons, a potential for the detection of circulating hormones and neuropeptides ( Histamine receptor signaling Histamine exerts its pleiotropic effects by binding to four subtypes of histamine receptors (HR), three of which are located within the brain (H1R, H2R, and H3R) ( Identified in 1966, the H1R subclass of histamine receptors (gene symbol: HRH1) primarily couples to Gq, resulting in the activation of the phospholipase C (PLC) signaling pathway ( Figure 2 )

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