9 – Dopamine Receptors

Publisher Summary Dopamine (DA) released from presynaptic nerve terminals elicits its effect through a family of G protein-coupled DA receptors. In the 1970s, it became evident that at least two classes of DA receptors (D1 and D2) were required to explain all the physiologic effects of DA and the pharmacologic profile of drugs blocking its actions. This traditional classification was mainly based on the ability of D1 receptors to stimulate the signal transduction enzyme adenylate cyclase, whereas D2 receptors either did not have an effect or inhibited it. The genomic organization of DA-receptor genes supports the idea that DA receptors have evolved from two distinct gene families, giving rise to D1-like and D2-like subfamilies. All DA receptors belong to a superfamily of G protein-coupled receptors (GPCRs) with seven transmembrane regions. D1-like receptors have a relatively short third cytoplasmic loop and long C-terminal tail, whereas D2-like receptors have a considerably longer third cytoplasmic loop and short C-terminal tail. These structural properties are common in many G protein-coupled receptors that stimulate and inhibit adenylate cyclase, respectively.