The histamine H₁ receptor is 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 (G_q) which activates phospholipase C and the phosphatidylinositol (PIP2) signalling pathway.

H₁ receptor and inflammation

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Neurophysiology

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Histamine H₁ receptors are activated by endogenous histamine, which is released by neurons which have their cell bodies in the tuberomamillary neurons of the hypothalamus. The histaminergic neurons of the tubero-mammillary nucleus become active during the 'wake' cycle, firing at approximately 2Hz; during slow wave sleep this firing rate drops to approximately 0.5Hz. Finally during REM sleep, histaminergic neurons stop firing all together. It has been reported that histaminergic neurons have the most wake-selective firing pattern of all known neuronal types (Passani et al., 2004).

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. (Reiner & Kamondi, 1994).

H1-receptor antagonists

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see Antihistamine - H1-receptor antagonists

References

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Passani, M. B., Lin, J. S., Hancock, A., Crochet, S., Blandina, P., 2004. The histamine H3 receptor as a novel therapeutic target for cognitive and sleep disorders. Trends Pharmacol Sci 25, 618-625.

Reiner P. B., Kamondi A., 1994. Mechanisms of antihistamine-induced sedation in the human brain: H1 receptor activation reduces a background leakage potassium current. Neuroscience 59(3), 579-88.

G protein coupled receptors