![[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}
|
|
|
|
|
||
P Ernsberger, TH Damon, LM Graff, SG Schafer and MO Christen
Department of Medicine and Neuroscience, Case Western Reserve School of Medicine, Cleveland, Ohio.
Both the hypotension and the sedation elicited by centrally acting antihypertensive agents are traditionally attributed to activation of alpha 2 adrenergic receptors. Second-generation centrally acting agents such as moxonidine are less sedating but retain antihypertensive efficacy. A novel receptor which recognizes imidazolines may contribute to their vasodepressor action in the ventrolateral medulla (VLM). We sought to determine whether moxonidine was a selective ligand for these putative I1-imidazoline receptors in different species and tissues. Moxonidine inhibited [3H]clonidine binding to bovine VLM membranes in a heterogeneous manner, showing 40-fold selectivity for one component. Masking studies using selective inhibitors to block either I1- imidazoline or alpha 2 sites established that the population of sites showing high affinity for moxonidine were I1-imidazoline sites. Moxonidine also showed 70-fold selectivity for I1-imidazoline sites labeled by [125I]p-iodoclonidine in the VLM. Moxonidine competitively inhibited [3H]clonidine binding to I1-imidazoline sites at concentrations that failed to inhibit alpha 2 binding. In the rat renal medulla, moxonidine showed almost 700-fold selectivity for I1- imidazoline sites relative to the alpha 2B receptor subtype. The high affinity of moxonidine for I1 sites was confirmed by using membranes prepared from bovine adrenomedullary cells, which lack alpha 2 adrenergic receptors. Among centrally acting antihypertensives, clinical potency correlated with binding affinity at bovine VLM I1- imidazoline sites (r = 0.996, N = 4), but not with alpha 2 adrenergic affinity (r = -0.239, N = 6). The potent action of moxonidine on I1- imidazoline receptors may account for its antihypertensive efficacy.
This article has been cited by other articles:
|
|
 |
|
  L.-G. Wang, J. Zeng, W.-J. Yuan, D.-F. Su, and W.-Z. Wang Cardiovascular Control: Comparative study of NMDA and AMPA/kainate receptors involved in cardiovascular inhibition produced by imidazoline-like drugs in anaesthetized rats Exp Physiol, September 1, 2007; 92(5): 849 - 858. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Sun and P. Ernsberger Marked Insulin Resistance in Obese Spontaneously Hypertensive Rat Adipocytes Is Ameliorated by in Vivo but Not in Vitro Treatment with Moxonidine J. Pharmacol. Exp. Ther., February 1, 2007; 320(2): 845 - 852. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Tanabe, Y. Kino, M. Honda, and H. Ono Presynaptic I1-Imidazoline Receptors Reduce GABAergic Synaptic Transmission in Striatal Medium Spiny Neurons J. Neurosci., February 8, 2006; 26(6): 1795 - 1802. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Kagawa, Y. Hayashi, I. Itoh, M. Iwasaki, K. Takada, T. Kamibayashi, A. Yamatodani, and T. Mashimo Identification of the Central Imidazoline Receptor Subtype Involved in Modulation of Halothane-Epinephrine Arrhythmias in Rats Anesth. Analg., December 1, 2005; 101(6): 1689 - 1694. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. El-Mas and A. A. Abdel-Rahman Differential modulation by estrogen of {alpha}2-adrenergic and I1-imidazoline receptor-mediated hypotension in female rats J Appl Physiol, October 1, 2004; 97(4): 1237 - 1244. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Velliquette and P. Ernsberger Contrasting Metabolic Effects of Antihypertensive Agents J. Pharmacol. Exp. Ther., December 1, 2003; 307(3): 1104 - 1111. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Velliquette and P. Ernsberger The Role of I1-Imidazoline and {alpha}2-Adrenergic Receptors in the Modulation of Glucose Metabolism in the Spontaneously Hypertensive Obese Rat Model of Metabolic Syndrome X J. Pharmacol. Exp. Ther., August 1, 2003; 306(2): 646 - 657. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Raasch, B. Jungbluth, U. Schafer, W. Hauser, and P. Dominiak Modification of Noradrenaline Release in Pithed Spontaneously Hypertensive Rats by I1-Binding Sites in Addition to alpha 2-Adrenoceptors J. Pharmacol. Exp. Ther., March 1, 2003; 304(3): 1063 - 1071. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Schafer, C. Burgdorf, A. Engelhardt, T. Kurz, and G. Richardt Presynaptic Effects of Moxonidine in Isolated Buffer Perfused Rat Hearts: Role of Imidazoline-1 Receptors and alpha 2-Adrenoceptors J. Pharmacol. Exp. Ther., December 1, 2002; 303(3): 1163 - 1170. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Y. Sy, V. Bruban, P. Bousquet, and J. Feldman Nitric Oxide and Central Antihypertensive Drugs : One More Difference Between Catecholamines and Imidazolines Hypertension, February 1, 2001; 37(2): 246 - 249. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Poisson, M.-O. Christen, and F. Sannajust Protective Effects of I1-Antihypertensive Agent Moxonidine against Neurogenic Cardiac Arrhythmias in Halothane-Anesthetized Rabbits J. Pharmacol. Exp. Ther., June 1, 2000; 293(3): 929 - 938. [Abstract] [Full Text]
|
|
|
|
|
|
C. A. Fairbanks and G. L. Wilcox Moxonidine, a Selective alpha 2-Adrenergic and Imidazoline Receptor Agonist, Produces Spinal Antinociception in Mice J. Pharmacol. Exp. Ther., July 1, 1999; 290(1): 403 - 412. [Abstract] [Full Text]
|
|
|
|
|
|
M. M. El-Mas and A. A. Abdel-Rahman Ethanol Counteraction of I1-Imidazoline but Not Alpha-2 Adrenergic Receptor-Mediated Reduction in Vascular Resistance in Conscious Spontaneously Hypertensive Rats J. Pharmacol. Exp. Ther., February 1, 1999; 288(2): 455 - 462. [Abstract] [Full Text]
|
|
|
|
|
|
R. R. Wenzel, L. Spieker, S. Qui, S. Shaw, T. F. Luscher, and G. Noll I1-Imidazoline Agonist Moxonidine Decreases Sympathetic Nerve Activity and Blood Pressure in Hypertensives Hypertension, December 1, 1998; 32(6): 1022 - 1027. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Liu and I. M. Coupar Involvement of Alpha-2 Adrenoceptors in the Effects of Moxonidine on Intestinal Motility and Fluid Transport J. Pharmacol. Exp. Ther., December 1, 1997; 283(3): 1367 - 1374. [Abstract] [Full Text]
|
|
|
|
 |
|
 P. Ernsberger and M. A. Haxhiu The I1-imidazoline-binding site is a functional receptor mediating vasodepression via the ventral medulla Am J Physiol Regulatory Integrative Comp Physiol, November 1, 1997; 273(5): R1572 - R1579. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G Li, S Regunathan, C. Barrow, J Eshraghi, R Cooper, and D. Reis Agmatine: an endogenous clonidine-displacing substance in the brain Science, February 18, 1994; 263(5149): 966 - 969. [Abstract] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
