Fyziologie histamínu a jeho význam v organismu
H1 receptor
CNS
- Dendrites of the output neurons of the histaminergic tuberomammillary nucleus
- Projects to the dorsal raphe, locus coeruleus, and additional structures.
- Sleep-wake cycle (promotes wakefulness)
- Body temperature
- Nociception
- Endocrine homeostasis
- Regulates appetite
- Involved in cognition [1]
Periphery
- Smooth muscle
- Endothelium
- Sensory nerves
- Causes bronchoconstriction, bronchial smooth muscle contraction
- Vasodilation
- Promotes hypernociception (visceral hypersensitivity)
- Involved in itch perception and urticaria [1]
H4 receptor
- Primarily on basophils
- Bone marrow
- Expressed in the thymus
- Small intestine
- Spleen
- Colon
- Mast cell chemotaxis
- Itch perception
- Cytokine production and secretion
- Visceral hypersensitivity
- Inflammation, allergy, cognition, etc.) have not been fully characterized
Ligand-gated ion channel
- Histamine-gated chloride channel
- CNS (hypothalamus, thalamus)
- Fast inhibitory postsynaptic potentials
- Intestinal epithelium
- Chloride secretion (associated with secretory diarrhea) [1]
Cévní permeabilita
- Vascular hyperpermeability and vasodilation
- Histamine binding to endothelial cells causes them to contract
- Increasing vascular leak
- Stimulates synthesis and release of various vascular smooth muscle cell relaxants
- Nitric oxide
- Endothelium-derived hyperpolarizing factors
- Resulting in blood vessel dilation
- Key role in the pathophysiology of anaphylaxis [1]
Gastric acid release
- Enterochromaffin-like cells
- Located within the gastric glands of the stomach
- Release histamine that stimulates nearby parietal cells
- By binding to the apical H2 receptor
- Stimulation of the parietal cell induces
- Uptake of carbon dioxide and water from the blood
- Converted to carbonic acid by the enzyme carbonic anhydrase
- Inside the cytoplasm of the parietal cell, the carbonic acid
- Readily dissociates into hydrogen and bicarbonate ions
- Bicarbonate ions diffuse back through the basilar membrane and into the bloodstream
- Hydrogen ions are pumped into the lumen of the stomach via a K+/H+ ATPase pump
- Histamine release is halted when the pH of the stomach starts to decrease [1]
H2 receptor
CNS
- Dorsal striatum (caudate nucleus and putamen)
- Cerebral cortex (external layers)
- Hippocampal formation
- Dentate nucleus of the cerebellum
- Most known H2 receptor ligands are unable to cross the blood–brain barrier in sufficient concentrations to allow for neuropsychological and behavioral testing [1]
Periphery
- Parietal cells
- Vascular smooth muscle cells
- Neutrophils
- Mast cells
- Cells in the heart and uterus
- Vasodilation
- Stimulation of gastric acid secretion
- Modulates gastrointestinal function [1]
- žaludku
- Stimulace vede k sekreci HCl
- Ranitidin (H2-blokátory) blokují tyto receptory a snižují sekreci HCl [3]
H3 receptor
Central nervous system + Peripheral nervous system tissue
- Autoreceptor and heteroreceptor functions
- Decreased neurotransmitter release of histamine, acetylcholine, norepinephrine, serotonin
- Modulates
- Nociception
- Gastric acid secretion
- Food intake [1]
Receptory
- G protein-coupled histamine receptors
- H1- H4
- Activate ligand-gated chloride channels in the brain and intestinal epithelium [1]
Sleep-wake regulation
- Ascending reticular activating system
- Released from histaminergic neurons
- Which project out of the mammalian hypothalamus
- Posterior hypothalamus known as the tuberomammillary nucleus (TMN)
- histamine neurons in this region comprise the brain's histamine system
- Projects widely throughout the brain
- Includes axonal projections to the cortex, medial forebrain bundle, and elsewhere
- Involved in regulating the sleep-wake cycle
- Promote arousal when activated
- Neural firing rate of histamine neurons in the TMN
- Strongly positively correlated with an individual's state of arousal.
- Fire rapidly during periods of wakefulness
- More slowly during periods of relaxation/tiredness
- Stop firing altogether during REM and NREM (non-REM) sleep [1]
- Local immune responses
- Function in the gut
- Neurotransmitter for the brain, spinal cord, and uterus
- Inflammatory response
- Mediator of itching
- Part of an immune response to foreign pathogens
- Produced by basophils
- Mast cells
- Found in nearby connective tissues
- Increases the permeability of the capillaries to white blood cells and some proteins
- Způsobuje intenzivní kontrakce dělohy
- Stah plicních průdušinek
- Vzniká otok
- Ke snížení krevního tlaku
- Produkci kyseliny chlorovodíkové z parietálních buněk
- Minoritní neurotransmiter v mozku
