Histamine exerts its effects by binding to four types of histamine receptors, all of which are G protein-coupled receptors (GPCRs):
H₁ Receptor
H₂ Receptor
H₃ Receptor
H₄ Receptor
Each receptor subtype has distinct distributions and functions in the body.
H₁ Receptor (Histamine Receptor)
Mechanism:
Coupled to Gq proteins; activates phospholipase C, leading to increased intracellular calcium.
Functions:
Vasodilation: Causes dilation of blood vessels, increasing blood flow and redness.
Increased Vascular Permeability: Leads to edema and swelling.
Bronchoconstriction: Constriction of airway smooth muscles, affecting breathing.
Sensory Nerve Stimulation: Causes itching and pain.
Distribution:
Smooth Muscles: Respiratory tract, gastrointestinal tract.
Endothelial Cells: Lining of blood vessels.
CNS Neurons: Involved in sleep-wake regulation, appetite, and cognition.
Immune Cells: T cells, B cells, eosinophils.
H₂ Receptor
Mechanism:
Coupled to Gs proteins; stimulates adenylate cyclase, increasing cyclic AMP (cAMP).
Functions:
Gastric Acid Secretion: Stimulates parietal cells to secrete hydrochloric acid.
Cardiac Effects: Increases heart rate and contractility.
Smooth Muscle Relaxation: Vasodilation in blood vessels.
Immunomodulation: Inhibits antibody synthesis and T-cell proliferation.
Distribution:
Gastric Parietal Cells: Stomach lining.
Cardiac Muscle: Heart tissue.
Vascular Smooth Muscle: Blood vessels.
CNS: Neurons regulating various functions.
H₃ Receptor
Mechanism:
Coupled to Gi/o proteins; inhibits adenylate cyclase, decreasing cAMP.
Functions:
Neurotransmitter Release Inhibition: Modulates release of histamine, acetylcholine, norepinephrine, and serotonin.
Autoreceptor Function: Regulates histamine synthesis and release in neurons.
Distribution:
CNS: Predominantly in the brain, affecting sleep, appetite, and cognition.
Peripheral Nervous System: Sensory neurons.
H₄ Receptor
Mechanism:
Coupled to Gi/o proteins; similar signaling pathways as H₃ receptors.
Functions:
Chemotaxis: Attracts immune cells like eosinophils and mast cells to sites of inflammation.
Immunomodulation: Influences cytokine production and immune cell activation.
Distribution:
Bone Marrow: Hematopoietic cells.
Immune Cells: Mast cells, eosinophils, dendritic cells.
Spleen and Thymus: Involved in immune responses.
Distribution of Histamine Receptors in the Human Body
Receptor | Location | Primary Functions |
|---|---|---|
H₁ | - Smooth muscles (bronchi, GI tract)- Endothelium- CNS neurons- Immune cells | - Allergic response- Bronchoconstriction- Vasodilation- Sensory nerve stimulation |
H₂ | - Gastric parietal cells- Heart- Vascular smooth muscle- CNS neurons | - Gastric acid secretion- Cardiac stimulation- Vasodilation- Immunomodulation |
H₃ | - CNS neurons- Peripheral nerves | - Neurotransmitter release inhibition- Sleep regulation |
H₄ | - Bone marrow- Immune cells (mast cells, eosinophils)- Spleen- Thymus | - Chemotaxis of immune cells- Modulation of immune response |