JPET Assistant Professor of Medicine (Clinician-Educator)

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Barrett, R. J.
Right arrow Articles by Wright, K. F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Barrett, R. J.
Right arrow Articles by Wright, K. F.

Discrimination of A1 versus A2 receptor subtype selectivity of adenosine receptor agonists in vivo

RJ Barrett, DA Droppleman and KF Wright

Department of Pharmacology, Whitby Research, Inc., Richmond, Virginia.

Previous attempts to discern and quantify the selectivity of agonists for A1 versus A2 adenosine receptors in vivo have been confounded by the activation of baroreceptor reflexes and/or simultaneous expression of responses to both A1 and A2 receptor activation. In anesthetized, vagotomized rats with isolated in situ constant-flow perfused hindquarters (HQ), bradycardic responses to i.v. agonist injections measured A1 receptor activation and HQ vasodilation elicited by i.a. agonist injections measured the stimulation of A2 receptors. Adenosine and 5'-N-ethylcarboxamidoadenosine (NECA) produced A2 receptor-mediated HQ vasodilation at doses 8- and 4-fold lower (-log ED50 values, 7.3 +/- 0.04 mol and 8.7 +/- 0.06 mol, respectively) than those required to evoke A1 receptor-mediated bradycardia (-log ED50 values, 6.4 +/- 0.01 mol and 8.1 +/- 0.07 mol, respectively). N6-cyclopentyladenosine (CPA) was approximately 8-fold selective for A1 receptors (-log ED50 values, A1, 8.5 +/- 0.05 mol; A2, 7.6 +/- 0.16 mol). 2-(Phenylamino)adenosine (CV-1808) and 2[2(4-fluorophenyl)ethoxy]adenosine (FPEA) were at least 125- and 200-fold more potent agonists at A2 receptors (-log ED50 values, 7.7 +/- 0.10 mol and 8.0 +/- 0.24 mol, respectively) than at A1 receptors (-log ED50 values, 5.6 +/- 0.08 mol and 5.7 +/- 0.01 mol, respectively). These studies demonstrated that stimulation of A1 and A2 receptors may be discriminated in vivo and that such responses are selective, reproducible, dose-dependent and quantifiable.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 268, Issue 3, pp. 1166-1173, 03/01/1994
Copyright © 1994 by American Society for Pharmacology and Experimental Therapeutics




This article has been cited by other articles:


Home page
 Mol. Pharmacol.Home page
M. Koyama, N. Seyedi, W.-P. Fung-Leung, T. W. Lovenberg, and R. Levi
Norepinephrine Release from the Ischemic Heart Is Greatly Enhanced in Mice Lacking Histamine H3 Receptors
Mol. Pharmacol., February 1, 2003; 63(2): 378 - 382.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
N. Seyedi, T. Win, H. M. Lander, and R. Levi
Bradykinin B2-Receptor Activation Augments Norepinephrine Exocytosis From Cardiac Sympathetic Nerve Endings : Mediation by Autocrine/Paracrine Mechanisms
Circ. Res., November 19, 1997; 81(5): 774 - 784.
[Abstract] [Full Text]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1994 by the American Society for Pharmacology and Experimental Therapeutics.