G Proteins and Animal Models of Parkinson’s Disease

G protein-linked receptor function and regulation have received considerable attention owing to the pivotal role of these receptors in mediating cellular responses to chemical transmitters. Typically, alterations in neurotransmitter status can either result in reduced receptor activity, also known as receptor desensitization, or increased receptor activity, referred to as receptor supersensitivity. Receptor desensitization has perhaps been best characterized in the (3-adrenergic receptor system, where prolonged treatment with β-receptor agonists results in the decreased number and sensitivity of β-adrenergic receptors (Hadcock and Malbon, 1993). Although the role of G proteins and other signal transduction components in regulating receptor desensitization has long been appreciated, the study of receptor supersensitivity has generally focused more narrowly on changes in receptor levels and affinity. Receptor supersensitivity can be brought about in a number of ways, most commonly by receptor antagonist treatment or through denervation (Srivastava and Mishra, 1994). In both cases, the dopamine receptor system has received a great deal of attention and is generally accepted as the prototype for the study of receptor supersensitivity. The purpose of this chapter is to discuss the potential role of G proteins in mediating dopamine receptor supersensitivity.