In<unk> umans,<unk>  exerts its effects primarily by binding to G protein-coupled<unk>  receptors, designated<unk> 1 through<unk> 4. As of 2015,<unk>  is believed to activate ligand-gated chloride channels in the brain and intestinal epithelium. + Biological targets of<unk>  in the<unk> uman body Location Function Sources receptor CNS: Expressed on the dendrites of the output neurons of the<unk> rgic tuberomammillary nucleus, which projects to the dorsal raphe, locus coeruleus, and additional structures. Periphery: Smooth muscle, endothelium, mast cells , sensory nerves CNS: Sleep-wake cycle (promotes wakefulness), body temperature, nociception, endocrine<unk> omeostasis, regulates appetite, involved in cognition Periphery: Causes bronchoconstriction, bronchial smooth muscle contraction, urinary bladder contractions, vasodilation, promotes<unk> ypernociception (visceral<unk> ypersensitivity), involved in itch perception and urticaria. receptor CNS: Dorsal striatum (caudate nucleus and putamen), cerebral cortex (external layers),<unk> ippocampal formation, dentate nucleus of the cerebellum Periphery: Located on parietal cells, vascular smooth muscle cells, neutrophils, mast cells, as well as on cells in the<unk> eart and uterus CNS: Not established (note: most known<unk> 2 receptor ligands are unable to cross the blood–brain barrier in sufficient concentrations to allow for neuropsychological and behavioral testing) Periphery: Primarily involved in vasodilation and stimulation of gastric acid secretion. Urinary bladder relaxation. Modulates gastrointestinal function. receptor Located in the central nervous system and to a lesser extent peripheral nervous system tissue Autoreceptor and<unk> eteroreceptor functions: decreased neurotransmitter release of<unk> , acetylcholine, norepinephrine, serotonin. Modulates nociception, gastric acid secretion, and food intake. receptor Located primarily on basophils and in the bone marrow. It is also expressed in the thymus, small intestine, spleen, and colon. Plays a role in mast cell chemotaxis, itch perception, cytokine production and secretion, and visceral<unk> ypersensitivity. Other putative functions (e.g., inflammation, allergy, cognition, etc.)<unk> ave not been fully characterized. Ligand-gated ion channel Location Function Sources Putatively: CNS <unk> ypothalamus, thalamus) and intestinal epithelium Brain: Produces fast inhibitory postsynaptic potentials Intestinal epithelium: chloride secretion (associated with secretory diarrhea)
Histamine
Leukotriene
Serotonin
Nitric oxide
Antileukotriene
Defensin
Acetylcholine
Interleukin