Pharmacological properties of histamine receptor subtypes
Arrang, J.M.
Cellular and Molecular Biology 40(3): 275-281
1994
ISSN/ISBN: 0145-5680 PMID: 7920174 Document Number: 433068
Histamine, a ubiquitous cell-to-cell messenger, exerts its numerous actions through interaction with three pharmacologically distinct receptor subtypes, termed H-1, H-2 and H-3. The design of selective agonists and antagonists has allowed to establish their respective pharmacological profile. Radioligand binding studies and, very recently, molecular biological studies have shown that they all belong to the superfamily of G-protein coupled receptors. H-1 and H-2-receptor antagonists have been successfully used for a long time in the treatment of allergy and ulcer, respectively. Some of them have been designed as highly potent and selective radioligands and have allowed to analyze the precise distribution of H-1 and H-2 receptors in various tissues including the brain. Recently, H-1- and H-2-receptor genes have been cloned in various animal species. Transfection of mammalian cells with these intronless genes has confirmed the respective coupling of H-1 and H-2 receptors with phospholipase C and adenylylcyclase. However, other known or unknown intracellular signals, could also be triggered by the stimulation in a transfected cell of a single H-1 or H-2 receptor through coupling to different G-proteins. A third histamine receptor subtype, the H-3 receptor was evidenced in rodent and human brain by the inhibition of histamine release and synthesis it mediates in various areas. Thus, H-3 receptors were considered as autoreceptors localized on histaminergic terminals. With the design of several potent and selective H-3-receptor agonists and of an antagonist thioperamide, the critical role of H-3 receptors in the control of histaminergic neurons in vivo was established. Using these ligands, the role of histamine acting as a neurotransmitter in the control of arousal was confirmed, and several novel actions and physiological roles of histamine in the brain and peripheral tissues could be unravelled.