Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
GoGreen Membership

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 14 August 1992:
Vol. 257. no. 5072, pp. 977 - 980
DOI: 10.1126/science.1354394
Prev | Table of Contents | Next

Articles

Science, Vol 257, Issue 5072, 977-980
Copyright © 1992 by American Association for the Advancement of Science

articles

A point mutation of the alpha 2-adrenoceptor that blocks coupling to potassium but not calcium currents

A Surprenant, DA Horstman, H Akbarali, and LE Limbird

Vollum Institute, Oregon Health Sciences University, Portland 97201.

The alpha 2A-adrenergic receptor (adrenoceptor) was stably expressed in AtT20 mouse pituitary tumor cells; adrenoceptor agonists inhibited adenylyl cyclase, inhibited voltage-dependent calcium currents, and increased inwardly rectifying potassium currents. An aspartic acid residue (Asp79) highly conserved among guanine nucleotide-binding protein (G protein)-coupled receptors was mutated to asparagine; in cells transfected with the mutant alpha 2-receptor, agonists inhibited adenylyl cyclase and calcium currents but did not increase potassium currents. Because distinct G proteins appear to couple adrenoceptors to potassium and calcium currents, the present findings suggest that the mutant alpha 2-adrenoceptor cannot achieve the conformation necessary to activate G proteins that mediate potassium channel activation.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Two "Knockout" Mouse Models Demonstrate That Aortic Vasodilatation Is Mediated via {alpha}2A-Adrenoceptors Located on the Endothelium.
M. M. Shafaroudi, M. McBride, C. Deighan, A. Wokoma, J. Macmillan, C. J. Daly, and J. C. McGrath (2005)
J. Pharmacol. Exp. Ther. 314, 804-810
   Abstract »    Full Text »    PDF »
Multiple Signaling States of G-Protein-Coupled Receptors.
D. M. Perez and S. S. Karnik (2005)
Pharmacol. Rev. 57, 147-161
   Abstract »    Full Text »    PDF »
Random Mutagenesis of the M3 Muscarinic Acetylcholine Receptor Expressed in Yeast: IDENTIFICATION OF SECOND-SITE MUTATIONS THAT RESTORE FUNCTION TO A COUPLING-DEFICIENT MUTANT M3 RECEPTOR.
B. Li, N. M. Nowak, S.-K. Kim, K. A. Jacobson, A. Bagheri, C. Schmidt, and J. Wess (2005)
J. Biol. Chem. 280, 5664-5675
   Abstract »    Full Text »    PDF »
Distinct Domains of the {micro}-Opioid Receptor Control Uncoupling and Internalization.
J. Celver, M. Xu, W. Jin, J. Lowe, and C. Chavkin (2004)
Mol. Pharmacol. 65, 528-537
   Abstract »    Full Text »    PDF »
Endothelial and Microvascular Function.
D. Striimper, M. Durieux, and P. Roekaerts (2003)
Seminars in Cardiothoracic and Vascular Anesthesia 7, 225-238
   Abstract »    PDF »
Heterozygous alpha 2A-adrenergic receptor mice unveil unique therapeutic benefits of partial agonists.
C. M. Tan, M. H. Wilson, L. B. MacMillan, B. K. Kobilka, and L. E. Limbird (2002)
PNAS 99, 12471-12476
   Abstract »    Full Text »    PDF »
Physiological significance of alpha 2-adrenergic receptor subtype diversity: one receptor is not enough.
M. Philipp, M. Brede, and L. Hein (2002)
Am J Physiol Regulatory Integrative Comp Physiol 283, R287-R295
   Abstract »    Full Text »    PDF »
Activation and Deactivation Kinetics of alpha 2A- and alpha 2C-Adrenergic Receptor-activated G Protein-activated Inwardly Rectifying K+ Channel Currents.
M. Bunemann, M. M. Bucheler, M. Philipp, M. J. Lohse, and L. Hein (2001)
J. Biol. Chem. 276, 47512-47517
   Abstract »    Full Text »    PDF »
Vascular Adrenoceptors: An Update.
S. Guimaraes and D. Moura (2001)
Pharmacol. Rev. 53, 319-356
   Abstract »    Full Text »    PDF »
The Role of a Conserved Inter-Transmembrane Domain Interface in Regulating {alpha}2a-Adrenergic Receptor Conformational Stability and Cell-Surface Turnover.
M. H. Wilson, H. A. Highfield, and L. E. Limbird (2001)
Mol. Pharmacol. 59, 929-938
   Abstract »    Full Text »
Characterization of Hyperpolarization-Activated Cation Currents in Mouse Anterior Pituitary, AtT20 D16:16 Corticotropes.
L. Tian and M. J. Shipston (2000)
Endocrinology 141, 2930-2937
   Abstract »    Full Text »    PDF »
Mechanisms regulating hypoxic respiratory depression during fetal and postnatal life.
J. M. Bissonnette (2000)
Am J Physiol Regulatory Integrative Comp Physiol 278, R1391-R1400
   Abstract »    Full Text »    PDF »
In Vivo Gene Modification Elucidates Subtype-Specific Functions of alpha 2-Adrenergic Receptors.
J. W. Kable, L. C. Murrin, and D. B. Bylund (2000)
J. Pharmacol. Exp. Ther. 293, 1-7
   Abstract »    Full Text »
Uncovering Molecular Mechanisms Involved in Activation of G Protein-Coupled Receptors.
U. Gether (2000)
Endocr. Rev. 21, 90-113
   Abstract »    Full Text »
Cannabinoid Receptors Can Activate and Inhibit G Protein-Coupled Inwardly Rectifying Potassium Channels in a Xenopus Oocyte Expression System.
S. D. McAllister, G. Griffin, L. S. Satin, and M. E. Abood (1999)
J. Pharmacol. Exp. Ther. 291, 618-626
   Abstract »    Full Text »
The Functional Microdomain in Transmembrane Helices 2 and 7 Regulates Expression, Activation, and Coupling Pathways of the Gonadotropin-releasing Hormone Receptor.
C. A. Flanagan, W. Zhou, L. Chi, T. Yuen, V. Rodic, D. Robertson, M. Johnson, P. Holland, R. P. Millar, H. Weinstein, et al. (1999)
J. Biol. Chem. 274, 28880-28886
   Abstract »    Full Text »    PDF »
A Mutation in the Second Transmembrane Region of the CB1 Receptor Selectively Disrupts G Protein Signaling and Prevents Receptor Internalization.
J. P. Roche, S. Bounds, S. Brown, and K. Mackie (1999)
Mol. Pharmacol. 56, 611-618
   Abstract »    Full Text »
Abnormal Regulation of the Sympathetic Nervous System in alpha 2A-Adrenergic Receptor Knockout Mice.
J. D. Altman, A. U. Trendelenburg, L. MacMillan, D. Bernstein, L. Limbird, K. Starke, B. K. Kobilka, and L. Hein (1999)
Mol. Pharmacol. 56, 154-161
   Abstract »    Full Text »
G Protein Regulation of Potassium Ion Channels.
M. Yamada, A. Inanobe, and Y. Kurachi (1998)
Pharmacol. Rev. 50, 723-757
   Abstract »    Full Text »    PDF »
P2Y2 Nucleotide Receptors Expressed Heterologously in Sympathetic Neurons Inhibit Both N-Type Ca2+ and M-Type K+ Currents.
A. K. Filippov, T. E. Webb, E. A. Barnard, and D. A. Brown (1998)
J. Neurosci. 18, 5170-5179
   Abstract »    Full Text »    PDF »
Mutation of a Highly Conserved Aspartate Residue in the Second Transmembrane Domain of the Cannabinoid Receptors, CB1 and CB2, Disrupts G-Protein Coupling.
Q. Tao and M. E. Abood (1998)
J. Pharmacol. Exp. Ther. 285, 651-658
   Abstract »    Full Text »
A Point Mutation (D79N) of the alpha 2A Adrenergic Receptor Abolishes the Antiepileptogenic Action of Endogenous Norepinephrine.
S. Janumpalli, L. S. Butler, L. B. MacMillan, L. E. Limbird, and J. O. McNamara (1998)
J. Neurosci. 18, 2004-2008
   Abstract »    Full Text »    PDF »
Nifedipine, an L-type Calcium Channel Blocker, Restores the Hypnotic Response in Rats Made Tolerant to the Alpha-2 Adrenergic Agonist Dexmedetomidine.
K. Reid, T.-Z. Guo, M. F. Davies, and M. Maze (1997)
J. Pharmacol. Exp. Ther. 283, 993-999
   Abstract »    Full Text »
Biochemical Basis of Partial Nephrogenic Diabetes Insipidus Phenotypes.
H. Sadeghi, G. L. Robertson, D. G. Bichet, G. Innamorati, and M. Birnbaumer (1997)
Mol. Endocrinol. 11, 1806-1813
   Abstract »    Full Text »
Substitution of a mutant alpha 2a-adrenergic receptor via "hit and run" gene targeting reveals the role of this subtype in sedative, analgesic, and anesthetic-sparing responses in vivo.
P. P. Lakhlani, L. B. MacMillan, T. Z. Guo, B. A. McCool, D. M. Lovinger, M. Maze, and L. E. Limbird (1997)
PNAS 94, 9950-9955
   Abstract »    Full Text »    PDF »
The µ-Opioid Receptor Down-Regulates Differently from the delta -Opioid Receptor: Requirement of a High Affinity Receptor/G Protein Complex Formation.
S. Chakrabarti, W. Yang, P.-Y. Law, and H. H. Loh (1997)
Mol. Pharmacol. 52, 105-113
   Abstract »    Full Text »
Somatostatin5 Receptor-Mediated [35S]Guanosine-5'-O-(3-thio)triphosphate Binding: Agonist Potencies and the Influence of Sodium Chloride on Intrinsic Activity.
A. J. Williams, A. D. Michel, W. Feniuk, and P. P. A. Humphrey (1997)
Mol. Pharmacol. 51, 1060-1069
   Abstract »    Full Text »
Subtype-Specific Intracellular Trafficking of alpha 2-Adrenergic Receptors.
D. A. Daunt, C. Hurt, L. Hein, J. Kallio, F. Feng, and B. K. Kobilka (1997)
Mol. Pharmacol. 51, 711-720
   Abstract »    Full Text »
Related Contribution of Specific Helix 2 and 7 Residues to Conformational Activation of the Serotonin 5-HT[IMAGE] Receptor.
S. C. Sealfon, L. Chi, B. J. Ebersole, V. Rodic, D. Zhang, J. A. Ballesteros, and H. Weinstein (1995)
J. Biol. Chem. 270, 16683-16688
   Abstract »    Full Text »    PDF »
Factors Determining Specificity of Signal Transduction by G-protein-coupled Receptors.
M. Sato, R. Kataoka, J. Dingus, M. Wilcox, J. D. Hildebrandt, and S. M. Lanier (1995)
J. Biol. Chem. 270, 15269-15276
   Abstract »    Full Text »    PDF »
The Regulator of G Protein Signaling RGS4 Selectively Enhances alpha 2A-Adreoreceptor Stimulation of the GTPase Activity of Go1alpha and Gi2alpha.
A. Cavalli, K. M. Druey, and G. Milligan (2000)
J. Biol. Chem. 275, 23693-23699
   Abstract »    Full Text »    PDF »


ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)