Imidazoleamines (part II)
Histamine
Where: Synthesized mostly in the brain and kidneys, used as neurotransmitter and hormone.
Effects:
- vasodilation and fall in blood pressure
- runny nose and waterey eyes
- difficulty breathing (bronchoconstriction)
- swelling / hives
- sneezing
- itching
- gastric acid secretion
- immune system modulation
- cognition
Histamine is a neurotransmitter that we humans have a love hate relationship with. It plays a role in over 23 different physiological functions, including the invocation of gastric acid secretion in our stomachs, contributing to allergic reactions, and playing an important role in many of immune responses. The chemical properties of histamine allow it to play a more diverse role within the body, properties such as coulombic (carry a charge), conformationality, and flexibility. Within the stomach histamine acts as a neurotransmitter and stimulates parietal cells to secrete gastric acid. Once stimulated the parietal cells uptake carbon dioxide and water from the blood in order to produce carbonic acid and secrete it into the stomach. During certain types of infections when a sensitized immune cells such as mast cells or basophils encounter a pathogen they will release histamine and other inflammatory chemicals to induce vasodilation. This allows other immune cells and resources from the blood stream to seep into the area of infection giving your immune system a massive advantage. However this is also where histamine sometimes works against us, during an allergic reaction the immune system overreacts to more or less harmless materials such as nuts or pollen. During allergies immune cells induce inflammation via histamine in much the same way which can often lead to swelling or even anaphylaxis. Histamine also impacts the nasal mucous membrane which is why many people that are allergic develop symptoms such as watery eyes, runny nose, sneezing, etc... This is due to the increased vascular permeability induced by histamine.
Typically histamine is released from granules within mast cells, antihistamines work by binding to histamine receptors thereby blocking histamine from binding to it's designated protein receptor. Humans have 4 main types of histamine receptors H1, H2, H3, and H4. When histamine binds to H1 and H2, various effects are possible depending on cell type and tissue location. Note that H3 and H4 are more complex and require an in depth understanding of neurology and immunology respectively, therefore they will not be covered thoroughly within this article.
H1:
- Peripheral sensory neurons: Causes itching and sometimes pain.
- Intestinal smooth muscle cells: Causes constriction, cramps, and possibly diarrhea. This is why some individuals that have severe allergic reactions can also develop stomach pains as well.
- Secretory mucosa (nasal passages and bronchial airways): Causes production of bronchi and nasal mucus, which leads to rhinorrhea (runny nose) and maybe cough.
- Pulmonary smooth muscle: Causes bronchosontriction (constriction of bronchioles) leading to decreased lung capacity (shortness of breath) and asthma. This part is especially relevant to anaphylaxis.
H1 and H2 receptor binding: (tissues that contain both receptors):
- Cardiovascular effects: Blood pressure (BP) drop due to induced vasodilation of arterioles and precapillary sphincters. The drop in BP leads to heart rate increase due to positively induced ionotropic and chronotropic effects (basically histamine acts on the heart and increases the strength and speed of contraction).
- Dermatologic effects: Vasodilation with increased permeability, with leakage of fluid and proteins into tissue. This can further result in symptoms such as the skin reddening, wheal / hive formation, irregular "halo" flare.
H2:
- Gastric effects: Stimulation of gastric acid secretion when H2 receptors on parietal cells within the stomach lining are activated. These cells secret more H+ leading to greater concentrations of gastric acid within the stomach when more histamine is present. A possible side effect of too much gastric acid secretion due to histamine is a gastric ulcer. A treatment for these types of ulcers are antihistamines known as H2 blockers that function by preventing the binding of histamine to H2 receptors found on parietal cells.
H3:
- CNS: Sleep/wake, cognition, neurotransmission. Histamine likely plays a role in keeping you awake which is why antihistamines can cause drowsiness.
H4:
- Various immune cells: Immune response modulation.
Other fascinating functions of histamine are it's involvement in sleep-wake regulation, sex, arousal, and possibly even the mechanisms related to how memories are forgotten. Additionally I also think it's noteworthy that histamine has also been found in relatively high concentrations in certain animal venoms and insect stings.
Continuation Introduction to monoamines Catecholamines (part III)...
