| Primary Identifier | IPR003980 | Type | Family |
| Short Name | Histamine_H3_rcpt |
| description | Histamine plays an important role in a variety of pathophysiological conditions. In allergic conditions, histamine is released from basophils and mast cells and is responsible for symptoms of allergic conditions of the skin and airways. In the gastric mucosa, gastric induced histamine release stimulates parietal cells to secrete gastric acid. In the central nervous system (CNS), histamine is synthesized in specific neurons that are localized in the posterior hypothalamus. These neurons are involved in a variety of important physiological functions, including the regulation of the sleep-wake cycle, cardiovascular control, regulation of the hypothalamic pituitary adrenal-axis, learning and memory [, , , , ].Histamine exerts its biological effects by binding to and activating four distinct separate rhodopsin-like G protein-coupled receptors-histamine H1 receptor, histamine H2 receptor, histamine H3 receptor, and histamine H4 receptor. Each of the histamine receptors produce a functional response, but their mechanism differs. The H1 receptor couples to Gq/11 stimulating phospholipase C, whereas the H2 receptor interacts with Gs to activate adenylyl cyclase []. The H3 and H4 receptors couple to Gi proteins to inhibit adenylyl cyclase, and to stimulate MAPK in the case of the H3 receptor [, ].This entry represents the histamine H3 receptor (also known as HH3R), which functions as presynaptic autoreceptor on histamine-containing neurones. The H3 receptor is expressed abundantly in the CNS, with highest levels found in the thalamus, caudate nucleus, cortex [, ], hypothalamus, hippocampus and olfactory tubercle. The diverse expression of H3 receptors throughout the cortex indicates an ability to modulate a large number of neurotransmitters such as acetylcholine, dopamine, GABA, norepinephrine and serotonin in the peripheral and CNS. However, H3 receptor distribution in the periphery is quite specific - low levels have been detected in the human small intestine, testis and prostate, but not in a number of other tissues tested, including the lung and spleen []. There has been some evidence of expression in the heart []and brain []. The ability to modulate neurotransmitters makes H3 receptors a novel therapeutic target to alleviate a number of conditions. These includes allergy, inflammatory disorders and numerous neurological conditions, such as obesity (because of the histamine/orexinergic system interaction), movement disorders (because of H3 receptor-modulation of dopamine and GABA in the basal ganglia), schizophrenia and ADHD (also because of dopamine modulation) and abnormal sleep/wake cycle (because of effects on noradrenaline, glutamate and histamine) [, , , , ]. Like all histamine receptors the H3 receptor is a G-protein coupled receptor. It is coupled to Gi, which leads to inhibition of cAMP formation []. |
