Histamine H1 receptor

The H1 receptor is a is_associated_with::histamine receptor belonging to the family of Rhodopsin-like is_associated_with::G-protein-coupled receptors. This receptor, which is activated by the is_associated_with::biogenic amine is_associated_with::histamine, is expressed throughout the body, to be specific, in is_associated_with::smooth muscles, on vascular is_associated_with::endothelial cells, in the heart, and in the is_associated_with::central nervous system. The H1 receptor is linked to an intracellular is_associated_with::G-protein (Gq) that activates phospholipase C and the is_associated_with::phosphatidylinositol (PIP2) signaling pathway. is_associated_with::Antihistamines, which act on this receptor, are used as anti-allergy drugs. The crystal structure of the receptor has been determined (shown on the right) and used to discover new histamine H1 receptor ligands in structure-based virtual screening studies.

Role in inflammation
The production of prostaglandin E2 synthase induces the release of histamine from neurons, causing systemic vasodilation, along with increased cell permeability due to its action on H1 receptors.

Neurophysiology
Histamine H1 receptors are activated by endogenous histamine, which is released by neurons that have their cell bodies in the is_associated_with::tuberomammillary nucleus of the is_associated_with::hypothalamus. The histaminergic neurons of the tuberomammillary nucleus become active during the 'wake' cycle, firing at approximately 2 Hz; during is_associated_with::slow wave sleep, this firing rate drops to approximately 0.5 Hz. Finally, during REM sleep, histaminergic neurons stop firing altogether. It has been reported that histaminergic neurons have the most wake-selective firing pattern of all known neuronal types.

In the cortex, activation of H1 receptors leads to inhibition of cell membrane is_associated_with::potassium channels. This depolarizes the neurons and increases the resistance of the neuronal cell membrane, bringing the cell closer to its firing threshold and increasing the excitatory voltage produced by a given excitatory current. H1 receptor antagonists, or is_associated_with::antihistamines, produce drowsiness because they oppose this action, reducing neuronal excitation.