GPCRs adrenergic receptors

G Protein-Coupled Receptors (GPCRs) ttiA Adrenergic Receptor Dopamine D3 Receptor Endothelin A Receptor... 

A further consideration is that receptors which primarily activate one pathway may, on occasion, activate a second pathway (Fig. 10-10). An example is the ability of GPCRs, such as a2-adrenergic receptors or mAChRs, to activate the MAPK cascade. Activation of adenylyl cyclase-linked receptors results in the release of G protein Py subunits, which, probably via an intermediary protein tyrosine kinase (PTK-X), stimulates phosphorylation of the adaptor protein SHC [36]. This in turn recruits the Grb2-SOS complex and activates the MAPK pathway. 

GPCR Antitarget Pharmacophore Modeling The ana Adrenergic Receptor... 

In case of the P -adrenergic receptor, phosphorylation of serine and threonine residues in the carboxyl tail can be shown to be involved in desensitization and internalization (141,156). Other GPCRs—such as the p- and 5-opioid receptors... 

In some cases, for example, in the case of the P -adrenergic receptor, internalization has been found to be a precursor to resensitization of the receptor (168,169). This phenomenon may be common to many GPCRs. Internalization may afford the opportunity of receptor dephosphorylation through the action of an endosomic acid phosphatase (170), resulting in resensitization of the receptor (171). 

The residues required for internalization, like those implicated in desensitization motifs, do not always meet the requirements for putative sites of kinase-mediated phosphorylation. Among the numerous motifs that have been implicated, an NPXXY motif (154,173) may be required for agonist-induced activation and inter-nahzation of the p -adrenergic receptor, and a dileucine motif in the carboxyl tail of many GPCRs (154) may be involved in internalization of receptors such as the Pj-adrenergic (174) and the vasopressin Via receptors (175). 

The postsynaptic S-adrenoceptors (jS-ARs) belong to the rhodopsin/ S2 adrenergic receptor-like receptors that belong to one of three major subfamilies of the GPCRs [83]. The S-AR family is subdivided into at least three discrete subtypes, the ySr, )S2-AR [84], and the atypical jSa-AR [85,86]. Additionally, a putative subtype has been identified in cardiac tissue, classified as the P4-AR [87], The P-]- and S2-AR are Gs-protein coupled, thereby elevating the intracellular level of cyclic adenosine monophosphate (cAMP) and causing positive inotropic and chronotropic effects [88]. The P2-AR can also couple to the Grprotein. 

The /3-adrenergic receptor is an integral protein with seven hydrophobic regions of 20 to 28 amino acid residues that snake back and forth across the plasma membrane seven times. This protein is a member of a very large family of receptors, all with seven transmembrane helices, that are commonly called serpentine receptors, G protein-coupled receptors (GPCR), or 7 transmembrane segment (7tm) receptors. The binding of epinephrine to a site on the... 

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