**11. Abbreviations**

28 Neuroscience – Dealing with Frontiers

unrelated to the initial stimulus. Certainly, this classification is only operational and both types of desensitization may occur simultaneously in the cells (García-Sáinz et al., 2000).

β-Adrenoceptor feedback regulation is common; however, β-receptors differ in the extent to which they can undergo such regulation, with the β2-receptors being the most susceptible. Upon challenge with an agonist, the β2-receptor couples to Gs and activates adenylyl cyclase to form cAMP. cAMP leads to stimulation of cyclic AMP-dependent protein kinases, like PKA, with consequent phosphorylation of β-receptor. That phosphorylation provides the signal for β-arrestin recruitment. Arrestins constitute a large family of widely expressed proteins (Baillie and Houslay, 2005, Westfall and Westfall, 2006). β-arrestin translocation from the cytosol to the activated β-receptor physically blocks the interaction of the receptor with its cellular effectors, presumably due to steric hindrance (Lefkowitz and Shenoy, 2005). The receptor phosphorylation followed by β-arrestin binding has been linked to subsequent endocytosis of the receptor. The capacity of β-arrestins to bind to the structural protein clathrin, initiating the internalization of phosphorylated receptors into vesicles, facilitates endocytosis (Goodman et al., 1996, Nelson et al., 2008). In addition to blunting responses that require the presence of the receptor on the surface of the cell, these regulatory processes may also contribute to novel mechanisms of receptor signalling via intracellular pathways

Receptor desensitization may also be mediated by second messenger feedback. For example, β-adrenoceptor-mediated cAMP accumulation leads to activation of PKA, which can phosphorylate residues of β-receptors, which results in their own inhibition. For the β2 receptor, phosphorylation occurs on serine residues both in the third cytoplasmic loop and in the carboxyl terminal tail of the receptor. β3-Receptors do not suffer down regulation, since they lack recognition sites for the cAMP dependent kinases activated by stimulation of

Although less addressed, α-receptors desensitization has gained increased interest (García-Sáinz et al., 2000). Current data indicate that the decrease in receptor activity is associated with a homologous desensitization mechanism. The activation of PKC by Gq-coupled receptors may lead to phosphorylation of this class of G protein-coupled receptors. That phosphorylation constitutes a very substantial sterical impediment for the effective interaction of receptors with G proteins. Receptor phosphorylation is associated with

In the case of α-receptors heterologous desensitization, it is not completely clear whether kinases, arrestins, or other molecules play the main role (García-Sáinz et al., 2000). However, activated PKA or PKC may phosphorylate any structurally similar receptor with the appropriate consensus sites for phosphorylation, a process which is considered a heterologous desensitization (Gainetdinov et al., 2004, Hoffmann, 2004).11. Summary

The autonomic nervous system is considered responsible for organ specific adjustments to the environment, while the endocrine system regulates more generalized adaptations by releasing hormones into the systemic circulation that act on "distant places" (Westfall and Westfall, 2006). NA and ADR play crucial roles in the interaction between the autonomic and endocrine systems when the body has to adjust to several and varied situations. It is of outmost importance that their roles and all the participants in the "adrenergic" system are

receptor internalization and β-arrestins are involved (García- Sáinz et al., 2000).

Even so, the mechanisms are equally complex and need further characterization.

(Baillie and Houslay, 2005).

β-adrenoceptors (Gauthier et al., 1996).

Adrenaline; Epinephrine (ADR); Adenosine-5'-triphosphate (ATP); Adenosine triphosphatase (ATPase); Calcium ion (Ca2+); Ca2+/calmodulin-dependent protein kinase II (CaMKII); Cyclic adenosine monophosphate (cAMP); Catechol-*O*-methyltransferase (COMT); Dihydroxyphenylglycol (DHPG); Deoxyribonucleic acid (DNA); Inhibitory G protein (Gi); Stimulatory G protein (Gs); 5-Hydroxytriptamine; Serotonin (5-HT); Homovanillic acid (HVA); Potassium ion (K+); Half-saturation constant; Michaelis constant (Km); Monoamine oxidase (MAO); Magnesium ion (Mg2+); Sodium ion (Na+); Noradrenaline; Norepinephrine (NA); Noradrenaline transporter (NET); Superoxide anion (O2●–); Organic cation transporters (OCT); Hydroxyl radical (HO●); Phenylethanolamine Nmethyltransferase; Noradrenaline N-methyltransferase (PMNT); Ribonucleic acid (RNA); Vanillylmandelic acid; Methoxy-4-hydroxymandelic acid (VMA); Vesicular monoamine transporter (VMAT).
