This post is part of a series on the pharmacology of histamine. The main histamine physiologic effects on H1 and H2 receptors will be discussed here as an introduction to antihistamines drug therapy and its clinical uses.
Histamine physiology: actions on tissues
Histamine is an autacoid (molecule secreted locally to increase or decrease the activity of nearby cells) synthesized from the amino acid histidine. Histamine actions are mediated by the activation of four receptor subtypes: H1, H2, H3 and H4, all of them G protein-coupled receptors. Currently only H1 and H2 receptors have clinical interest, but research on H3 and H4 receptors is being conducted.
The following figure summarizes histamine actions on different tissues such as bronchial smooth muscle, intestinal smooth muscle, bowel peristalsis and gastric mucosa.
Source: Lullman, H. Color Atlas of Pharmacology. Thieme, 2005.
Bronchial smooth muscle
Histamine causes contraction of bronchial smooth muscle, thus narrowing the airways. Asthmatic patients may be up to 1,000 times more sensitive to histamine mediated bronchoconstriction than individuals not affect by the disease.
Intestinal smooth muscle
Histamine activation of H1 receptors produces constrictiction of intestinal smooth muscle, which results in increased bowel peristalsis and diarrhea.
Peripheral nervous endings
Histamine stimulates sensory nerve endings, especially those mediating pain and itching. This effect, mediated by H1 receptors, is responsible for pain and itch after an injury such as insect bite.
Histamine enhances Ca2+ influx into cardiac myocytes, this leads to minor increases in heart inotropism (force of contraction) and in chronotropism (rate of contraction).
Histamine increases production of nasal and bronchial mucus, resulting in respiratory symptoms.
Edema and inflammation
Histamine acts especially on H1 receptors in the poscapillary vessels. The activation of H1 receptors produces contraction that leads to separation of endothelial cells, which allows the transudation of fluid and plasma proteins into the perivascular tissue. The clinical correlates of this phenomenon are urticaria and edema. This makes histamine a key mediator in the inflammatory response.
Through activation of H2 receptors, histamine potentiates gastrin-induced acid secretion. H2 receptor activation enhances the production of second messenger adenosine monophosphate (cAMP) by adenyl cyclase. As you can see in the figure, the other molecules involved in gastric hydrochloric acid secretion are gastrin and acethylcholine. H2 blockers, such as ranitidine, are drugs commonly used in the treatment of ulcers and heartburn.
Golan, David E (editor). “Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy”, 2nd edition. LWW: 2008.
Harvey, Richard; Champe, Pamela (series editors). “Lippincott illustrated reviews: Pharmacology”, 4th edition. LWW: 2009.
Lullmann, Heinz; Mohr Klaus. “Color Atlas of Pharmacology”, 2nd edition. Thieme: 1999.
Katzung, B. “Basic & Clinical Pharmacology”, 10th Edition. Mc Graw Hill Medical: 2007