![[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}
|
|
|
|
|
||
DB Bylund, C Ray-Prenger and TJ Murphy
Department of Pharmacology, School of Medicine, University of Missouri, Columbia.
The affinities of 34 adrenergic antagonists for alpha-2 adrenergic receptors were determined from homogenate radioligand binding studies using [3H]yohimbine and [3H]rauwolscine. It has been suggested that alpha-2 adrenergic receptors can be subdivided into alpha-2A and alpha- 2B subtypes. Oxymetazoline is selective for alpha-2A receptors, whereas prazosin is alpha-2B selective. Five different tissues were used, each of which has only one of the two subtypes: human platelet (alpha-2A), HT29 cell line (alpha-2A), human cerebral cortex (alpha-2A), neonatal rat lung (alpha-2B), and NG108-15 cell line (alpha-2B). The drug affinities were highly correlated when alpha-2A tissues were compared with alpha-2A tissues (r = 0.97 to 0.98) or when the two alpha-2B tissues were compared (r = 0.99). By contrast, comparison of an alpha- 2A tissue with an alpha-2B tissue resulted in poor correlations (r = 0.77 to -0.87). Three new subtype selective drugs were identified among these drugs on the basis of at least a 10-fold greater affinity for one subtype. All three were selective for the alpha-2B subtype: ARC-239 (100-fold selective), chlorpromazine (18-fold selective), and 7- hydroxychlorpromazine (17-fold selective). These studies, by demonstrating distinct pharmacological profiles for the two alpha-2 adrenergic receptor subtypes in several different tissues, further support the existence and definition of these subtypes. The identification of a cell line for each subtype should be useful in the further study of alpha-2 adrenergic receptor subtypes.
This article has been cited by other articles:
|
|
 |
|
  T.-C. Chou Theoretical Basis, Experimental Design, and Computerized Simulation of Synergism and Antagonism in Drug Combination Studies Pharmacol. Rev., September 1, 2006; 58(3): 621 - 681. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. N. Desai, S. Salim, K. M. Standifer, and D. C. Eikenburg Involvement of G Protein-Coupled Receptor Kinase (GRK) 3 and GRK2 in Down-Regulation of the {alpha}2B-Adrenoceptor J. Pharmacol. Exp. Ther., June 1, 2006; 317(3): 1027 - 1035. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Striimper, M. Durieux, and P. Roekaerts Endothelial and Microvascular Function Seminars in Cardiothoracic and Vascular Anesthesia, September 1, 2003; 7(3): 225 - 238. [Abstract] [PDF]
|
|
|
|
 |
|
 Y.-Z. Pan, D.-P. Li, and H.-L. Pan Inhibition of Glutamatergic Synaptic Input to Spinal Lamina IIo Neurons by Presynaptic alpha 2-Adrenergic Receptors J Neurophysiol, April 1, 2002; 87(4): 1938 - 1947. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Khalid, Y. Giudicelli, and J.-P. Dausse An Up-Regulation of Renal alpha 2A-Adrenoceptors Is Associated with Resistance to Salt-Induced Hypertension in Sabra Rats J. Pharmacol. Exp. Ther., December 1, 2001; 299(3): 928 - 933. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Li and J. C. Eisenach alpha 2A-Adrenoceptor Stimulation Reduces Capsaicin-Induced Glutamate Release from Spinal Cord Synaptosomes J. Pharmacol. Exp. Ther., December 1, 2001; 299(3): 939 - 944. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Sun, S. Lockyer, J. Li, R. Chen, M. Yoshitake, and J.-I. Kambayashi OPC-28326, a Selective Femoral Vasodilator, Is an alpha 2C-Adrenoceptor-Selective Antagonist J. Pharmacol. Exp. Ther., November 1, 2001; 299(2): 652 - 658. [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]
|
|
|
|
 |
|
 I. Limon-Boulez, R. Bouet-Alard, T. W. Gettys, S. M. Lanier, J.-P. Maltier, and C. Legrand Partial Agonist Clonidine Mediates {alpha}2-AR Subtypes Specific Regulation of cAMP Accumulation in Adenylyl Cyclase II Transfected DDT1-MF2 Cells Mol. Pharmacol., February 1, 2001; 59(2): 331 - 338. [Abstract] [Full Text]
|
|
|
|
|
|
H. Greney, P. Ronde, C. Magnier, F. Maranca, C. Rascente, W. Quaglia, M. Giannella, M. Pigini, L. Brasili, C. Lugnier, et al. Coupling of I1 Imidazoline Receptors to the cAMP Pathway: Studies with a Highly Selective Ligand, Benazoline Mol. Pharmacol., June 1, 2000; 57(6): 1142 - 1151. [Abstract] [Full Text]
|
|
|
|
|
|
E. S. Vizi Role of High-Affinity Receptors and Membrane Transporters in Nonsynaptic Communication and Drug Action in the Central Nervous System Pharmacol. Rev., March 1, 2000; 52(1): 63 - 90. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. M. L. W. Keularts, R. M. A. van Gorp, M. A. H. Feijge, W. M. J. Vuist, and J. W. M. Heemskerk alpha 2A-Adrenergic Receptor Stimulation Potentiates Calcium Release in Platelets by Modulating cAMP Levels J. Biol. Chem., January 21, 2000; 275(3): 1763 - 1772. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. B. Bylund and D. M. Chacko Characterization of {alpha}2 Adrenergic Receptor Subtypes in Human Ocular Tissue Homogenates Invest. Ophthalmol. Vis. Sci., September 1, 1999; 40(10): 2299 - 2306. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Zhang, V. Klimek, J. T. Farley, M.-Y. Zhu, and G. A. Ordway alpha 2C Adrenoceptors Inhibit Adenylyl Cyclase in Mouse Striatum: Potential Activation by Dopamine J. Pharmacol. Exp. Ther., June 1, 1999; 289(3): 1286 - 1292. [Abstract] [Full Text]
|
|
|
|
|
|
S. A. Aicher and C. T. Drake Clonidine Evokes Vasodepressor Responses via alpha 2-Adrenergic Receptors in Gigantocellular Reticular Formation J. Pharmacol. Exp. Ther., May 1, 1999; 289(2): 688 - 694. [Abstract] [Full Text]
|
|
|
|
 |
|
 K. P. Makaritsis, D. E. Handy, C. Johns, B. Kobilka, I. Gavras, and H. Gavras Role of the {alpha}2B-Adrenergic Receptor in the Development of Salt-Induced Hypertension Hypertension, January 1, 1999; 33(1): 14 - 17. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Kukkonen, A. Renvaktar, R. Shariatmadari, and K. E. O. Åkerman Ligand- and Subtype-Selective Coupling of Human Alpha-2 Adrenoceptors to Ca++ elevation in Chinese Hamster Ovary Cells J. Pharmacol. Exp. Ther., November 1, 1998; 287(2): 667 - 671. [Abstract] [Full Text]
|
|
|
|
|
|
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]
|
|
|
|
|
|
D. A. Daunt, C. Hurt, L. Hein, J. Kallio, F. Feng, and B. K. Kobilka Subtype-Specific Intracellular Trafficking of alpha 2-Adrenergic Receptors Mol. Pharmacol., May 1, 1997; 51(5): 711 - 720. [Abstract] [Full Text]
|
|
|
|
|
|
J. Nasman, C. C. Jansson, and K. E.O. Akerman The Second Intracellular Loop of the alpha 2-Adrenergic Receptors Determines Subtype-specific Coupling to cAMP Production J. Biol. Chem., April 11, 1997; 272(15): 9703 - 9708. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Mhaouty, J. Cohen-Tannoudji, R. Bouet-Alard, I. Limon-Boulez, J.-P. Maltier, and C. Legrand Characteristics of the [IMAGE][IMAGE]/[IMAGE][IMAGE]-Adrenergic Receptor-coupled Adenylyl Cyclase System in Rat Myometrium during Pregnancy J. Biol. Chem., May 5, 1995; 270(18): 11012 - 11016. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Grossman, H. K. Manji, and W. Z. Potter Platelet {alpha}2-adrenoreceptors in depression: a critical examination J Psychopharmacol, January 1, 1993; 7(1_suppl): 4 - 18. [Abstract] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
