A2A-Adrenergic receptors

Fig. 3. Signal transduction of the tt2A-D79N adrenergic receptor. Mutation of the aspartic acid residue 79 in the second transmembrane domain of the mouse a2A adrenergic receptor to asparagine (D79N) selectively uncoupled this receptor mutant from activation of currents in vitro without interfering with Ca channel or adenylyl cyclase inhibition (Surprenant et al. 1992). In vivo, the a2A D79N receptor was expressed at 20% of the level of the wild-type a2A-receptor (MacMillan et d. 1996), and Ca channel inhibition was also blunted (a) (Lakhlani et al. 1997)...

Makaritsis KP, Johns C, Gavras I, Altman JD, Handy DE, Bresnahan MR, Gavras H (1999) Sympathoinhibitory function of the a2A-adrenergic receptor subtype. Hypertension 34 403-407... 

Wang CD, Buck MA, Fraser CM (1991) Site-directed mutagenesis of a2A-adrenergic receptors identification of amino acids involved in iigand binding and receptor activation by agonists. Mol Pharmacol 40,168-179... 

Wilson MH, Limbird LE (2000) Mechanisms regulating the cell surface residence time of the a2A-adrenergic receptor, Biochem 39 693-700... 

Lakhlani, P. P., MacMillan, L. B., Guo, T. Z., McCool B. A., Lovinger, D. M., Maze, M., Limbird, L. E. Substitution of a mutant a2A-adrenergic receptor via hit and run gene targeting reveals the role of this subtype in sedative, analgesic, and anesthetic-sparing responses in vivo, Proc. Natl. Acad. Sci. USA 1997, 94, 9950-9955. 

Nikolaev, V. O., Hoffmann, C., Bunemann, M., Lohse, M. J., and Vilardaga, J. P. (2006b). Molecular basis of partial agonism at the neurotransmitter a2A adrenergic receptor and Gj-protein heterotrimer./. Biol. Chem. 281, 24506-24511. 

Stone LS, MacMillan LB, Kitto KF, Limbird LE, Wilcox GL (1997) The a2A adrenergic receptor subtype mediates spinal analgesia evoked by 02 agonists and is necessary for spinal adrenergic-opioid synergy. J Neurosci 17 7157-65... 

Talley EM, Rosin DL, Lee A, Guyenet PG, Lynch KR (1996) Distribution of a2A-adrenergic receptor-like immunoreactivity in the rat central nervous system. J Comp Neurol 372 111-34... 

Liang M, Eason MG, Jewell-Motz EA et al (1998) Phosphorylation and functional desensitisation of the a2A-adrenergic receptor by protein kinase C. Mol Pharmacol 54 44-9 Lim W, Kim SJ, Yan HD et al (1997) Ca2+-channel dependent and -independent inhibition of exocytosis by extracellular ATP in voltage-clamped rat adrenal chromaffin cells. Pflugers Arch 435 34 12... 

Macmillan LB, Hein L, Smith MS, Piascik MT, LimbirdLE. Central hypotensive effects of the a2a-adrenergic receptor subtype. Science 1996 273 801-803. 

Altman JD, Trendelenburg AU, Macmillan L, et al. Abnormal regulation of the sympathetic nervous system in a2A-adrenergic receptor knockout mice. Mol Pharmacol 1999 56 154-161. 

Chabre O, Conklin BR, Brandon S, Bourne HR, LimbirdLE. Coupling of the a2A-adrenergic receptor to multiple G-proteins—a simple approach for estimating receptor-G-protein coupling efficiency in a transient expression system. J Biol Chem 1994 269 5730-5734. 

Lakhlani PP, Lovinger DM, Limbird LE. Genetic evidence for involvement of multiple effector systems in a2A-adrenergic receptor inhibition of stimulus-secretion coupling. Mol Pharmacol 1996 50 96-103. 

Brink CB, Wade SM, Neubig RR. Agonist-directed trafficking of porcine a2A-adrenergic receptor signaling in Chinese hamster ovary cells 1-isoproterenol selectively activates Gs. J Pharmacol Exp Ther 2000 294 539-547. 

Chung DA, Wade SM, Fowler CB, et al. Mutagenesis and peptide analysis of the DRY motif in the a2A adrenergic receptor evidence for alternate mechanisms in G protein-coupled receptors. Biochem Biophys Res Commun 2002 293 1233-1241. 

Eason MG, Liggett SB. Chimeric mutagenesis of putative G-protein coupling domains of the a2A-adrenergic receptor - Localization of two redundant and fully competent Gi coupling domains. J Biol Chem 1996 271 12,826—12,832. 

Wade SM, Lim WK, Lan KL, Chung DA, Nanamori M, Neubig RR. Gj activator region of a2A-adrenergic receptors distinct basic residues mediate Gj versus Gs activation. Mol Pharmacol 1999 56 1005-1013. 

Gerhardt MA, Neubig RR. a2A-Adrenergic receptors (a2-AR) efficiently inhibit adenylate-cyclase in transfected CHO-K1 cells. FASEB J 1991 5 A1594-A1594. 

Marjamaki A, Pihlavisto M, Cockcroft V, Heinonen P, Savola JM, Scheinin M. Chloroethylclonidine binds irreversibly to exposed cysteines in the fifth membrane-spanning domain of the human a2A-adrenergic receptor. Mol Pharmacol 1998 53 370-376. 

Wang Q, Limbird LE. Regulated interactions of the a2A adrenergic receptor with spinophilin, 14-3-3 zeta, and arrestin 3. J Biol Chem 2002 277 50,589-50,596. 

Keefer JR, Limbird LE. The a2A-adrenergic receptor is targeted directly to the basolateral membrane domain of Madin-Darby canine kidney cells independent of coupling to pertussis toxin-sensitive GTP-binding proteins. J Biol Chem 1993 268 11,340-11,347. 

Keefer JR, Kennedy ME, Limbird LE. Unique structural features important for stabilization vs polarization of the a2A-adrenergic receptor on the basolateral membrane of Madin-Darby canine kidney cells. J Biol Chem 1994 269 16,425-lb,432. 

Eason MG, Jacinto MT, Theiss CT, Liggett SB. The palmitoylated cysteine of the cytoplasmic tail of a2A-adrenergic receptors confers subtype-specific agonist-promoted downregulation. Proc Natl Acad Sci USA 1994 91 11,178-11,182. 

Rosin DL, Zeng D, Stornetta RL, et al. Immunohistochemical localization of a2A-adrenergic receptors in catecholaminergic and other brainstem neurons in the rat. Neuroscience 1993 56 139-155. 

Wilson MH, Highfield HA, Limbird LE. The role of a conserved inter-transmembrane domain interface in regulating a2a-adrenergic receptor conformational stability and cell-surface turnover. Mol Pharmacol 2001 59 929-938. 

Tan CM, Wilson MH, MacMillan LB, Kobilka BK, Limbird LE. Heterozygous a2A adrenergic receptor mice unveil unique therapeutic benefits of partial agonists. Proc Natl Acad Sci USA 2002 99 12,471-12,476. 

Janumpalli S, Butler LS, MacMillan LB, Limbird LE, McNamara JO. A point mutation (D79N) of the a2A adrenergic receptor abolishes the antiepilep-togenic action of endogenous norepinephrine. J Neurosci 1998 18 2004-2008. 

Schramm NL, McDonald MP, Limbird LE. The a2a-adrenergic receptor plays a protective role in mouse behavioral models of depression and anxiety. J Neurosci 2001 21 4875 1882. 

Lahdesmaki J, Sallinen J, MacDonald E, Kobilka BK, Fagerholm V, Scheinin M. B ehavioral and neurochemical characterization of a2A-adrenergic receptor knockout mice. Neuroscience 2002 113 289-299. 

Jordan BA, Gomes I, Rios C, Filipovska J, Devi LA. Functional interactions between mu opioid and a2A-adrenergic receptors. Mol Pharmacol 2003 64 1317— 1324. 

Guyenet PG, Stornetta RL, Riley T, Norton FR, Rosin DL, Lynch KR. a2A-Adrenergic receptors are present in lower brainstem catecholaminergic and serotonergic neurons innervating spinal cord. Brain Res 1994 638 285-294. 

---