Galanin receptor subtypes.

ABSTRACT

The potential for drug development in several therapeutic areas has made galanin receptors a popular target for the pharmaceutical industry in recent years. Galanin is present in brain tissue, as well as in peripheral tissues including the gastrointestinal tract, pancreas, bladder and genital tract. In general agreement with the results of immunohistochemical studies of galanin localization, galanin binding sites are found in many regions of the brain. The galanin receptor, a glycoprotein with a molecular mass of 54-60 kDa, was initially identified and characterized by radioligand binding studies with membranes prepared from tissues and cell lines. Several lines of evidence supported the existence of multiple galanin receptors, and at least four subtypes could be discriminated based on pharmacological data. Three galanin receptor subtypes, denoted GalR1, GalR2 and GalR3 (or GALR1, GALR2 and GALR3), have been cloned. Use of these cloned subtypes will allow compound screening, which will likely lead to the identification of compounds with high potency and selectivity for specific subtypes, providing powerful tools in studies of function, structure and regulation of galanin and its receptor subtypes. The next stage of the research in the galanin area will be to establish associations of therapeutic targets such as obesity, nociception and mnemonic processes with specific GalR subtypes. In addition, the generation of novel GalR antagonists/agonists that are bioavailable and subtype-selective will greatly accelerate the research efforts in this important field.