Histamine H1 receptor

The H1 receptor is a histamine receptor, and thus an important target for clinically important drugs, and is likely one of the most important receptors for modulating mammalian circadian cycles.

Histamine H1 receptor are metabotropic G-protein-coupled receptors expressed throughout the body, specifically in smooth muscles, on vascular endothelial cells, in the heart, and in the central nervous system. The H1 receptor is linked to an intracellular G-protein (Gq) that activates phospholipase C and the phosphatidylinositol (PIP2) signaling pathway.

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 tuberomamillary nucleus of the hypothalamus. The histaminergic neurons of the tuberomammillary nucleus become active during the 'wake' cycle, firing at approximately 2 Hz; during 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 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 antihistamines, produce drowsiness because they oppose this action, reducing neuronal excitation.