Biomaterial Database

One hundred years of histamine research. 2010

Katherine Figueroa, and Nigel Shankley

Johnson & Johnson Pharmaceutical Research and Development L.L.C., Merryfield Row, San Diego, California, USA. kfiguero@its.jnj.com

In this introductory chapter, we revisit some of the landmarks in the history of histamine research. Since histamine was first synthesized (1907) and isolated as a bacterial contaminant of an extract of ergot (1910), the elucidation of its role in health and disease and its molecular mechanism of action have been continuous, reflecting the application of advances in scientific knowledge, technology and therapeutics over the last 100 years. It appears that the research will continue indefinitely as the nature of the problem is inherently fractal. First, there was a single chemical entity, described in terms of state-of-the-art, two-dimensional projections of structures introduced by Fischer in 1891, and an idea that such potent chemicals produced their effects on biological systems as a consequence of an exquisite interaction with a receptive substance, the revolutionary concept of Langley (1905). Today, we recognize four receptor subtypes with multiple activation states and multiple coupling to intracellular effector systems, so that we are no longer able to reliably and in all instances classify compounds interacting with the histamine receptors simply as agonists or antagonists. The complexity is potentially overwhelming, but the promise of value to patients beyond that already provided by the first approved generations of histamine receptor blockers is a compelling driver.

UI	MeSH Term	Description	Entries
D011968	Receptors, Histamine	Cell-surface proteins that bind histamine and trigger intracellular changes influencing the behavior of cells. Histamine receptors are widespread in the central nervous system and in peripheral tissues. Three types have been recognized and designated H1, H2, and H3. They differ in pharmacology, distribution, and mode of action.	Histamine Binding Sites,Histamine Receptors,Histamine Receptor,Binding Sites, Histamine,Receptor, Histamine,Sites, Histamine Binding
D006632	Histamine	An amine derived by enzymatic decarboxylation of HISTIDINE. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter.	Ceplene,Histamine Dihydrochloride,Histamine Hydrochloride,Peremin
D006633	Histamine Antagonists	Drugs that bind to but do not activate histamine receptors, thereby blocking the actions of histamine or histamine agonists. Classical antihistaminics block the histamine H1 receptors only.	Antihistamine,Antihistamines,Histamine Antagonist,Antagonist, Histamine,Antagonists, Histamine
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D015398	Signal Transduction	The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.	Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D049672	History, 19th Century	Time period from 1801 through 1900 of the common era.	19th Century History,19th Cent. History (Medicine),19th Cent. History of Medicine,19th Cent. Medicine,Historical Events, 19th Century,History of Medicine, 19th Cent.,History, Nineteenth Century,Medical History, 19th Cent.,Medicine, 19th Cent.,19th Cent. Histories (Medicine),19th Century Histories,Cent. Histories, 19th (Medicine),Cent. History, 19th (Medicine),Century Histories, 19th,Century Histories, Nineteenth,Century History, 19th,Century History, Nineteenth,Histories, 19th Cent. (Medicine),Histories, 19th Century,Histories, Nineteenth Century,History, 19th Cent. (Medicine),Nineteenth Century Histories,Nineteenth Century History
D049673	History, 20th Century	Time period from 1901 through 2000 of the common era.	20th Century History,20th Cent. History (Medicine),20th Cent. History of Medicine,20th Cent. Medicine,Historical Events, 20th Century,History of Medicine, 20th Cent.,History, Twentieth Century,Medical History, 20th Cent.,Medicine, 20th Cent.,20th Cent. Histories (Medicine),20th Century Histories,Cent. Histories, 20th (Medicine),Cent. History, 20th (Medicine),Century Histories, 20th,Century Histories, Twentieth,Century History, 20th,Century History, Twentieth,Histories, 20th Cent. (Medicine),Histories, 20th Century,Histories, Twentieth Century,History, 20th Cent. (Medicine),Twentieth Century Histories,Twentieth Century History
D049674	History, 21st Century	Time period from 2001 through 2100 of the common era.	21st Century History,21st Cent. History (Medicine),21st Cent. History of Medicine,21st Cent. Medicine,Historical Events, 21st Century,History of Medicine, 21st Cent.,History, Twenty-first Century,Medical History, 21st Cent.,Medicine, 21st Cent.,21st Cent. Histories (Medicine),21st Cent. Medicines,21st Century Histories,Cent. Histories, 21st (Medicine),Cent. History, 21st (Medicine),Cent. Medicine, 21st,Cent. Medicines, 21st,Century Histories, 21st,Century Histories, Twenty-first,Century History, 21st,Century History, Twenty-first,Histories, 21st Cent. (Medicine),Histories, 21st Century,Histories, Twenty-first Century,History, 21st Cent. (Medicine),History, Twenty first Century,Medicines, 21st Cent.,Twenty-first Century Histories,Twenty-first Century History
D020033	Protein Isoforms	Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.	Isoform,Isoforms,Protein Isoform,Protein Splice Variant,Splice Variants, Protein,Protein Splice Variants,Isoform, Protein,Isoforms, Protein,Splice Variant, Protein,Variant, Protein Splice,Variants, Protein Splice