H1 receptors

Detailed article on H1 receptors

The H1 receptor is a G protein-coupled receptor (GPCR) that binds histamine, a biogenic amine involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. The H1 receptor is one of four histamine receptors, the others being H2, H3, and H4.

Structure

The H1 receptor is a member of the GPCR family, characterized by seven transmembrane alpha-helices. The receptor is encoded by the HRH1 gene located on chromosome 3 in humans. The receptor's structure allows it to interact with histamine and initiate a signal transduction cascade via the Gq/11 protein.

Function

H1 receptors are primarily involved in mediating the effects of histamine in allergic reactions and inflammatory responses. When histamine binds to the H1 receptor, it activates the Gq/11 protein, which in turn activates phospholipase C (PLC). This leads to the production of inositol trisphosphate (IP3) and diacylglycerol (DAG), resulting in increased intracellular calcium levels and activation of protein kinase C (PKC).

The physiological effects of H1 receptor activation include:

• Contraction of smooth muscles, such as those in the bronchi and gastrointestinal tract.
• Increased vascular permeability, leading to edema.
• Stimulation of sensory nerve endings, causing itching and pain.
• Modulation of circadian rhythms and wakefulness.

Clinical Significance

H1 receptors are the target of antihistamines, which are used to treat allergic reactions, such as hay fever, urticaria, and anaphylaxis. First-generation antihistamines, such as diphenhydramine, can cross the blood-brain barrier and cause sedation. Second-generation antihistamines, such as loratadine, are less likely to cause sedation as they do not readily cross the blood-brain barrier.

Pharmacology

H1 receptor antagonists, commonly known as antihistamines, are classified into first-generation and second-generation based on their ability to cross the blood-brain barrier. First-generation antihistamines are more lipophilic and can cause central nervous system effects, including sedation. Second-generation antihistamines are more selective for peripheral H1 receptors and have fewer central side effects.

Research

Recent studies have explored the role of H1 receptors in the central nervous system, particularly in the regulation of sleep-wake cycles and cognitive functions. There is ongoing research into the development of more selective H1 receptor antagonists with improved efficacy and safety profiles.

Also see

• Histamine
• Antihistamine
• G protein-coupled receptor
• Allergic reaction
• H2 receptor
• H3 receptor
• H4 receptor