![[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}
|
|
|
|
|
||
TL Theroux, TA Esbenshade, RD Peavy and KP Minneman
Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
We compared the efficiencies with which human alpha 1-adrenergic receptor (AR) subtypes activate inositol phosphate (InsP) formation and increase intracellular Ca2+ in transfected cell lines. Expression of human alpha 1a-, alpha 1b-, and alpha 1d-AR cDNAs under the repressible control of anhydrotetracycline in human embryonic kidney (HEK) 293 cells, which normally express no alpha 1-ARs, was used to compare responses to norepinephrine (NE) at different receptor densities. Maximal NE-stimulated InsP formation was found to increase with increasing density of each subtype, whereas basal levels and responses to sodium fluoride did not change. A comparison of multiple subclones over equivalent ranges of receptor expression showed that activation of each subtype resulted in different maximal responses (alpha 1a > alpha 1b > alpha 1d) in HEK 293 cells. Analogous studies were carried out in human SK-N-MC cells, which normally express low levels of all three alpha 1-AR subtypes, using an isopropyl-beta-D-thiogalactoside- inducible expression system. Induction with isopropyl-beta-D- thiogalactoside increased the density of individual alpha 1-AR subtypes by 4-6-fold over the level of endogenous expression. Increased expression of each of these subtypes in SK-N-MC cells did not alter the EC50 value for NE in stimulating InsP formation or releasing [Ca2+]i but did increase maximal responses to NE. Similar to our findings in HEK 293 cells, a comparison of responses at similar expression levels in SK-N-MC cells showed different maximal responses stimulated by each subtype, for both InsP (alpha 1a > alpha 1b > or = alpha 1d) and [Ca2+]i (alpha 1a > alpha 1b > alpha 1d) responses. These studies show that agonist-occupied human alpha 1-AR subtypes have different efficiencies in activating phospholipase C in human cell lines. In both HEK 293 and SK-N-MC cells, alpha 1a-ARs couple most efficiently, whereas alpha 1d-ARs couple very poorly.
This article has been cited by other articles:
|
|
 |
|
  E. A. Woodcock, X.-J. Du, M. E. Reichelt, and R. M. Graham Cardiac {alpha}1-adrenergic drive in pathological remodelling Cardiovasc Res, February 1, 2008; 77(3): 452 - 462. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Suzuki, S. Morishima, T. Tanaka, and I. Muramatsu Snapin, a New Regulator of Receptor Signaling, Augments {alpha}1A-Adrenoceptor-operated Calcium Influx through TRPC6 J. Biol. Chem., October 5, 2007; 282(40): 29563 - 29573. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Hague, S. E. Lee, Z. Chen, S. C. Prinster, R. A. Hall, and K. P. Minneman Heterodimers of {alpha}1B- and {alpha}1D-Adrenergic Receptors Form a Single Functional Entity Mol. Pharmacol., January 1, 2006; 69(1): 45 - 55. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. C. Prinster, C. Hague, and R. A. Hall Heterodimerization of G Protein-Coupled Receptors: Specificity and Functional Significance Pharmacol. Rev., September 1, 2005; 57(3): 289 - 298. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Hague, L. S. Bernstein, S. Ramineni, Z. Chen, K. P. Minneman, and J. R. Hepler Selective Inhibition of {alpha}1A-Adrenergic Receptor Signaling by RGS2 Association with the Receptor Third Intracellular Loop J. Biol. Chem., July 22, 2005; 280(29): 27289 - 27295. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Uberti, C. Hague, H. Oller, K. P. Minneman, and R. A. Hall Heterodimerization with {beta}2-Adrenergic Receptors Promotes Surface Expression and Functional Activity of {alpha}1D-Adrenergic Receptors J. Pharmacol. Exp. Ther., April 1, 2005; 313(1): 16 - 23. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Chen, G. Rogge, C. Hague, D. Alewood, B. Colless, R. J. Lewis, and K. P. Minneman Subtype-selective Noncompetitive or Competitive Inhibition of Human {alpha}1-Adrenergic Receptors by {rho}-TIA J. Biol. Chem., August 20, 2004; 279(34): 35326 - 35333. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Hague, M. A. Uberti, Z. Chen, R. A. Hall, and K. P. Minneman Cell Surface Expression of {alpha}1D-Adrenergic Receptors Is Controlled by Heterodimerization with {alpha}1B-Adrenergic Receptors J. Biol. Chem., April 9, 2004; 279(15): 15541 - 15549. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Hague, Z. Chen, A. S. Pupo, N. A. Schulte, M. L. Toews, and K. P. Minneman The N Terminus of the Human {alpha}1D-Adrenergic Receptor Prevents Cell Surface Expression J. Pharmacol. Exp. Ther., April 1, 2004; 309(1): 388 - 397. [Abstract] [Full Text]
|
|
|
|
|
|
M. Israilova, T. Tanaka, F. Suzuki, S. Morishima, and I. Muramatsu Pharmacological Characterization and Cross Talk of {alpha}1A- and {alpha}1B-Adrenoceptors Coexpressed in Human Embryonic Kidney 293 Cells J. Pharmacol. Exp. Ther., April 1, 2004; 309(1): 259 - 266. [Abstract] [Full Text]
|
|
|
|
|
|
S. L. Kirstein and P. A. Insel Autonomic Nervous System Pharmacogenomics: A Progress Report Pharmacol. Rev., March 1, 2004; 56(1): 31 - 52. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Uberti, R. A. Hall, and K. P. Minneman Subtype-Specific Dimerization of {alpha}1-Adrenoceptors: Effects on Receptor Expression and Pharmacological Properties Mol. Pharmacol., December 1, 2003; 64(6): 1379 - 1390. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. A. Sharpe, L. Thomas, M. Loughnan, L. Motin, E. Palant, D. E. Croker, D. Alewood, S. Chen, R. M. Graham, P. F. Alewood, et al. Allosteric {alpha}1-Adrenoreceptor Antagonism by the Conopeptide {rho}-TIA J. Biol. Chem., September 5, 2003; 278(36): 34451 - 34457. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Lee, A. Robeva, Z. Chen, and K. P. Minneman Mutational Uncoupling of {alpha}1A-Adrenergic Receptors from G Proteins Also Uncouples Mitogenic and Transcriptional Responses in PC12 Cells J. Pharmacol. Exp. Ther., August 1, 2003; 306(2): 471 - 477. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Vicentic, A. Robeva, G. Rogge, M. Uberti, and K. P. Minneman Biochemistry and Pharmacology of Epitope-Tagged alpha 1-Adrenergic Receptor Subtypes J. Pharmacol. Exp. Ther., July 1, 2002; 302(1): 58 - 65. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Chalothorn, D. F. McCune, S. E. Edelmann, M. L. Garcia-Cazarin, G. Tsujimoto, and M. T. Piascik Differences in the Cellular Localization and Agonist-Mediated Internalization Properties of the alpha 1-Adrenoceptor Subtypes Mol. Pharmacol., May 1, 2002; 61(5): 1008 - 1016. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Mier, D. Kemken, H. A. Katus, G. Richardt, and T. Kurz Adrenergic activation of cardiac phospholipase D: role of {alpha}1-adrenoceptor subtypes Cardiovasc Res, April 1, 2002; 54(1): 133 - 139. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. A. Waldrop, D. Mastalerz, M. T. Piascik, and G. R. Post alpha 1B- and alpha 1D-Adrenergic Receptors Exhibit Different Requirements for Agonist and Mitogen-Activated Protein Kinase Activation to Regulate Growth Responses in Rat 1 Fibroblasts J. Pharmacol. Exp. Ther., January 1, 2002; 300(1): 83 - 90. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. T. Piascik and D. M. Perez alpha 1-Adrenergic Receptors: New Insights and Directions J. Pharmacol. Exp. Ther., August 1, 2001; 298(2): 403 - 410. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Guimaraes and D. Moura Vascular Adrenoceptors: An Update Pharmacol. Rev., June 1, 2001; 53(2): 319 - 356. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. H. Wang, X.-J. Du, D. J. Autelitano, C. A. Milano, and E. A. Woodcock Adverse effects of constitutively active alpha 1B-adrenergic receptors after pressure overload in mouse hearts Am J Physiol Heart Circ Physiol, September 1, 2000; 279(3): H1079 - H1086. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Pediani, J. F. MacKenzie, R. P. Heeley, C. J. Daly, and J. C. McGrath Single-Cell Recombinant Pharmacology: Bovine alpha 1a-Adrenoceptors in Rat-1 Fibroblasts Release Intracellular Ca2+, Display Subtype-Characteristic Agonism and Antagonism, and Exhibit an Antagonist-Reversible Inverse Concentration-Response Phase J. Pharmacol. Exp. Ther., June 1, 2000; 293(3): 887 - 895. [Abstract] [Full Text]
|
|
|
|
|
|
D. F. McCune, S. E. Edelmann, J. R. Olges, G. R. Post, B. A. Waldrop, D. J. J. Waugh, D. M. Perez, and M. T. Piascik Regulation of the Cellular Localization and Signaling Properties of the alpha 1B- and alpha 1D-Adrenoceptors by Agonists and Inverse Agonists Mol. Pharmacol., April 1, 2000; 57(4): 659 - 666. [Abstract] [Full Text]
|
|
|
|
|
|
J. Vazquez-Prado, L. del Carmen Medina, M. T. Romero-Avila, C. Gonzalez-Espinosa, and J. A. Garcia-Sainz Norepinephrine- and Phorbol Ester-induced Phosphorylation of alpha 1a-Adrenergic Receptors. FUNCTIONAL ASPECTS J. Biol. Chem., February 25, 2000; 275(9): 6553 - 6559. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Scheer, T. Costa, F. Fanelli, P. G. De Benedetti, S. Mhaouty-Kodja, L. Abuin, M. Nenniger-Tosato, and S. Cotecchia Mutational Analysis of the Highly Conserved Arginine within the Glu/Asp-Arg-Tyr Motif of the alpha 1b-Adrenergic Receptor: Effects on Receptor Isomerization and Activation Mol. Pharmacol., February 1, 2000; 57(2): 219 - 231. [Abstract] [Full Text]
|
|
|
|
|
|
D. J. J. Waugh, R. J. Gaivin, D. S. Damron, P. A. Murray, and D. M. Perez Binding, Partial Agonism, and Potentiation of alpha 1-Adrenergic Receptor Function by Benzodiazepines: A Potential Site of Allosteric Modulation J. Pharmacol. Exp. Ther., December 1, 1999; 291(3): 1164 - 1171. [Abstract] [Full Text]
|
|
|
|
|
|
O. Rossier, L. Abuin, F. Fanelli, A. Leonardi, and S. Cotecchia Inverse Agonism and Neutral Antagonism at alpha 1a- and alpha 1b-Adrenergic Receptor Subtypes Mol. Pharmacol., November 1, 1999; 56(5): 858 - 866. [Abstract] [Full Text]
|
|
|
|
|
|
S. L. Hrometz, S. E. Edelmann, D. F. McCune, J. R. Olges, R. W. Hadley, D. M. Perez, and M. T. Piascik Expression of Multiple alpha 1-Adrenoceptors on Vascular Smooth Muscle: Correlation with the Regulation of Contraction J. Pharmacol. Exp. Ther., July 1, 1999; 290(1): 452 - 463. [Abstract] [Full Text]
|
|
|
|
|
|
R. Z. Lin, J. Chen, Z.-W. Hu, and B. B. Hoffman Phosphorylation of the cAMP Response Element-binding Protein and Activation of Transcription by alpha 1 Adrenergic Receptors J. Biol. Chem., November 6, 1998; 273(45): 30033 - 30038. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Alexandrov, S. Keffel, M. Goepel, and M. C. Michel Stimulation of alpha 1A-Adrenoceptors in Rat-1 Cells Inhibits Extracellular Signal-Regulated Kinase by Activating p38 Mitogen-Activated Protein Kinase Mol. Pharmacol., November 1, 1998; 54(5): 755 - 760. [Abstract] [Full Text]
|
|
|
|
|
|
M. Yang, R. Büscher, K. Taguchi, B. Grübbel, P. A. Insel, and M. C. Michel Protein Kinase C Does Not Mediate Phenylephrine-Induced Down-regulation of Madin-Darby Canine Kidney Cell Alpha-1B Adrenoceptors J. Pharmacol. Exp. Ther., July 1, 1998; 286(1): 36 - 43. [Abstract] [Full Text]
|
|
|
|
|
|
X.-F. Deng, A. Sculptoreanu, S. Mulay, K. G. Peri, J.-F. Li, W.-H. Zheng, S. Chemtob, and D. R. Varma Crosstalk between Alpha-1A and Alpha-1B Adrenoceptors in Neonatal Rat Myocardium: Implications in Cardiac Hypertrophy J. Pharmacol. Exp. Ther., July 1, 1998; 286(1): 489 - 496. [Abstract] [Full Text]
|
|
 |
 |
 |
|
 |
 |
 |
