The potential role of D2 dopamine receptors as a target in the management of neuroendocrine tumors

Abstract

Dopamine is considered to be the main catecholamine neurotransmitter in the human central nervous system where it controls a variety of functions (cognition, emotion, hunger and satiety, locomotor activity) in addition to endocrine system regulation. Dopamine also plays multiple roles in the periphery as a modulator of cardiovascular and renal function, gastrointestinal motility, and the endocrine system.1,2 It exerts its functions via binding to dopamine receptors, which belong to a family of seven transmembrane domain G protein-coupled receptors, including 5 different receptor subtypes, D 1-D5.1,2 Members of the dopamine receptor family are encoded by genes at different chromosomal loci, but show a considerable homology in their protein structure and function. Analysis of dopamine receptor structure and function has suggested the existence of two different groups of receptors: D1-like, including the D1 and D5 receptors, generally associated with a stimulatory function; and D2-like, including the D2-D4 receptors, and generally associated with inhibitory functions.1 The D1 and D 5 receptors are encoded by genes lacking introns and share 80% homology in their transmembrane domains. The D2 receptor shares a 75% homology with the D3 and 53% homology with the D4 transmembrane domains and all three receptor subtypes are encoded by genes that are interrupted by introns.1 D2-like receptors have a long third intracellular loop, typical of receptors interacting with G-inhibitory (Gi) proteins, which are able to inhibit cyclic AMP production. The third intracellular loop is the region responsible for the G-protein coupling and signal transmission while the hydrophobic transmembrane domains are responsible for the binding of dopamine agonists and antagonists.1,2 ©2008 Landes Bioscience.