![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
R Link, D Daunt, G Barsh, A Chruscinski and B Kobilka
Department of Molecular and Cellular Physiology, Stanford University, California 94305.
Molecular cloning and ligand binding studies have shown the alpha 2 class of adrenergic receptor (alpha 2-AR) to be a family of at least three related subtypes in humans. These studies have not, however, identified distinct subtype-specific functions for these receptors in vivo. It should be possible to extend the analysis of alpha 2-AR subtype function to the animal level through the use of experimental mammalian embryology in mice. To begin this process, we have isolated two mouse genomic clones encoding alpha 2-AR subtypes and expressed these genes in COS-7 cells for binding studies. Sequence homology and ligand binding data allow the assignment of one clone (M alpha 2-4H) as the mouse homolog of the human alpha 2-C4 subtype. The other clone (M alpha 2-10H) closely resembles the human alpha 2-C10 subtype in sequence but binds with significantly lower affinity to yohimbine and rauwolscine, members of a distinct class of bulky alpha 2-selective antagonists commonly used to evaluate alpha 2-AR function in vivo. To define the domain(s) responsible for this unusual binding property, we constructed a series of M alpha 2-10H/human alpha 2-C10 chimeric receptors. Analysis of these receptors identified a conservative Cys201 to Ser201 change in the fifth transmembrane domain of M alpha 2-10H as being responsible for the low affinity of the mouse receptor for yohimbine.
This article has been cited by other articles:
|
|
 |
|
  M. Aihara, J. D. Lindsey, and R. N. Weinreb Effect on Diurnal Intraocular Pressure Variation of Eliminating the {alpha}-2 Adrenergic Receptor Subtypes in the Mouse Invest. Ophthalmol. Vis. Sci., March 1, 2008; 49(3): 929 - 933. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Braden and D. E. Nichols Assessment of the Roles of Serines 5.43(239) and 5.46(242) for Binding and Potency of Agonist Ligands at the Human Serotonin 5-HT2A Receptor Mol. Pharmacol., November 1, 2007; 72(5): 1200 - 1209. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Haskell, R. Horuk, M. Liang, M. Rosser, L. Dunning, I. Islam, L. Kremer, J. Gutierrez, G. Marquez, C. Martinez-A, et al. Identification and Characterization of a Potent, Selective Nonpeptide Agonist of the CC Chemokine Receptor CCR8 Mol. Pharmacol., January 1, 2006; 69(1): 309 - 316. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Horio, S. Teradaira, T. Imamura, R. V. P Anunciado, M. Kobayashi, T. Namikawa, and I. Niki The HND mouse, a nonobese model of type 2 diabetes mellitus with impaired insulin secretion Eur. J. Endocrinol., December 1, 2005; 153(6): 971 - 979. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. O. Ruuskanen, H. Xhaard, A. Marjamaki, E. Salaneck, T. Salminen, Y.-L. Yan, J. H. Postlethwait, M. S. Johnson, D. Larhammar, and M. Scheinin Identification of Duplicated Fourth {alpha}2-Adrenergic Receptor Subtype by Cloning and Mapping of Five Receptor Genes in Zebrafish Mol. Biol. Evol., January 1, 2004; 21(1): 14 - 28. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Philipp, M. Brede, and L. Hein Physiological significance of alpha 2-adrenergic receptor subtype diversity: one receptor is not enough Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2002; 283(2): R287 - R295. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. P. Naselsky, D. Ashton, R. R. Ruffolo Jr., and J. P. Hieble Rabbit alpha 2-Adrenoceptors: Both Platelets and Adipocytes Have alpha 2A-Pharmacology J. Pharmacol. Exp. Ther., July 1, 2001; 298(1): 219 - 225. [Abstract] [Full Text]
|
|
|
|
 |
|
 S. Guimaraes and D. Moura Vascular Adrenoceptors: An Update Pharmacol. Rev., June 1, 2001; 53(2): 319 - 356. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. J. Molderings, H. Bonisch, M. Bruss, J. Likungu, and M. Gothert Species-Specific Pharmacological Properties of Human {alpha}2A-Adrenoceptors Hypertension, September 1, 2000; 36(3): 405 - 410. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Chotani, S. Flavahan, S. Mitra, D. Daunt, and N. A. Flavahan Silent alpha 2C-adrenergic receptors enable cold-induced vasoconstriction in cutaneous arteries Am J Physiol Heart Circ Physiol, April 1, 2000; 278(4): H1075 - H1083. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Ambrosio, P. Molinari, S. Cotecchia, and T. Costa Catechol-Binding Serines of beta 2-Adrenergic Receptors Control the Equilibrium between Active and Inactive Receptor States Mol. Pharmacol., January 1, 2000; 57(1): 198 - 210. [Abstract] [Full Text]
|
|
|
|
 |
|
 T. Olli-Lahdesmaki, J. Kallio, and M. Scheinin Receptor Subtype-Induced Targeting and Subtype-Specific Internalization of Human alpha 2-Adrenoceptors in PC12 Cells J. Neurosci., November 1, 1999; 19(21): 9281 - 9288. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Salminen, M. Varis, T. Nyronen, M. Pihlavisto, A.-M. Hoffren, T. Lonnberg, A. Marjamaki, H. Frang, J.-M. Savola, M. Scheinin, et al. Three-dimensional Models of alpha 2A-Adrenergic Receptor Complexes Provide a Structural Explanation for Ligand Binding J. Biol. Chem., August 13, 1999; 274(33): 23405 - 23413. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Altman, A. U. Trendelenburg, L. MacMillan, D. Bernstein, L. Limbird, K. Starke, B. K. Kobilka, and L. Hein Abnormal Regulation of the Sympathetic Nervous System in alpha 2A-Adrenergic Receptor Knockout Mice Mol. Pharmacol., July 1, 1999; 56(1): 154 - 161. [Abstract] [Full Text]
|
|
|
|
 |
|
 L. HEIN, L. E. LIMBIRD, R. M. EGLEN, and B. K. KOBILKA Gene Substitution/Knockout to Delineate the Role of {alpha}2-Adrenoceptor Subtypes in Mediating Central Effects of Catecholamines and Imidazolines Ann. N.Y. Acad. Sci., June 21, 1999; 881(1): 265 - 271. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Björklund, J. Sirviö, J. Puoliväli, J. Sallinen, P. Jäkälä, M. Scheinin, B. K. Kobilka, and P. Riekkinen Jr. alpha 2C-Adrenoceptor-Overexpressing Mice Are Impaired in Executing Nonspatial and Spatial Escape Strategies Mol. Pharmacol., September 1, 1998; 54(3): 569 - 576. [Abstract] [Full Text]
|
|
|
|
|
|
D. E. Handy, C. Johns, M. R. Bresnahan, A. Tavares, M. Bursztyn, and H. Gavras Expression of {alpha}2-Adrenergic Receptors in Normal and Atherosclerotic Rabbit Aorta Hypertension, August 1, 1998; 32(2): 311 - 317. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Marjamäki, M. Pihlavisto, V. Cockcroft, P. Heinonen, J.-M. Savola, and M. Scheinin Chloroethylclonidine Binds Irreversibly to Exposed Cysteines in the Fifth Membrane-Spanning Domain of the Human alpha 2A-Adrenergic Receptor Mol. Pharmacol., March 1, 1998; 53(3): 370 - 376. [Abstract] [Full Text]
|
|
|
|
|
|
P. G. Guyenet Is the hypotensive effect of clonidine and related drugs due to imidazoline binding sites? Am J Physiol Regulatory Integrative Comp Physiol, November 1, 1997; 273(5): R1580 - R1584. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Klein, M. T. Ramirez, B. K. Kobilka, and M. von Zastrow A Novel Interaction between Adrenergic Receptors and the alpha -Subunit of Eukaryotic Initiation Factor 2B J. Biol. Chem., August 1, 1997; 272(31): 19099 - 19102. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. B. Bylund, L. J. Iversen, W. J. Matulka, and D. M. Chacko J. Pharmacol. Exp. Ther., June 1, 1997; 281(3): 1171 - 1177. [Abstract] [Full Text]
|
|
|
|
|
|
J. Sallinen, R. E. Link, A. Haapalinna, T. Viitamaa, M. Kulatunga, B. Sjöholm, E. Macdonald, M. Pelto-Huikko, T. Leino, G. S. Barsh, et al. Genetic Alteration of alpha 2C-Adrenoceptor Expression in Mice: Influence on Locomotor, Hypothermic, and Neurochemical Effects of Dexmedetomidine, a Subtype-Nonselective alpha 2-Adrenoceptor Agonist Mol. Pharmacol., January 1, 1997; 51(1): 36 - 46. [Abstract] [Full Text]
|
|
|
|
|
|
B. Cusack, K. Groshan, D. J. McCormick, Y.-P. Pang, R. Perry, C.-T. Phung, T. Souder, and E. Richelson Chimeric Rat/Human Neurotensin Receptors Localize a Region of the Receptor Sensitive to Binding of a Novel, Species-specific, Picomolar Affinity Peptide J. Biol. Chem., June 21, 1996; 271(25): 15054 - 15059. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Tavares, D. E. Handy, N. N. Bogdanova, D. L. Rosene, and H. Gavras Localization of {alpha}2A- and {alpha}2B-Adrenergic Receptor Subtypes in Brain Hypertension, March 1, 1996; 27(3): 449 - 455. [Abstract] [Full Text]
|
|
 |
 |
 |
|
 |
 |
 |
