Abstract Adenosine A 1 receptor antagonists have diuretic/natriuretic activity and may be useful for treating sodium-retaining diseases, many of which are associated with increased renal sympathetic tone. Therefore, it is important to determine whether A 1 receptor antagonists alter renal sympathetic neurotransmission. In isolated, perfused rat kidneys, renal vasoconstriction induced by renal sympathetic nerve simulation was attenuated by 1 ) 1,3-dipropyl-8-p-sulfophenylxanthine (xanthine analog that is a nonselective adenosine receptor antagonist, but is cell membrane impermeable and thus does not block intracellular phosphodiesterases), 2 ) xanthine amine congener (xanthine analog that is a selective A 1 receptor antagonist), 3 ) 1,3-dipropyl-8-cyclopentylxanthine (xanthine analog that is a highly selective A 1 receptor antagonist), and 4 ) FK453 (nonxanthine analog that is a highly selective A 1 receptor antagonist). In contrast, FR113452 (enantiomer of FK453 that does not block A 1 receptors), MRS-1754 (selective A 2B receptor antagonist), and VUF-5574 (selective A 3 receptor antagonist) did not alter responses to renal sympathetic nerve stimulation, and ZM-241385 (selective A 2A receptor antagonist) enhanced responses. Antagonism of A 1 receptors did not alter renal spillover of norepinephrine. 2-Chloro- N 6 -cyclopentyladenosine (highly selective A 1 receptor agonist) increased renal vasoconstriction induced by exogenous norepinephrine, an effect that was blocked by 1,3-dipropyl-8-cyclopentylxanthine, U73122 (phospholipase C inhibitor), GF109203X (protein kinase C inhibitor), PP1 (c-src inhibitor), wortmannin (phosphatidylinositol 3-kinase inhibitor), and OSU-03012 (3-phosphoinositide-dependent protein kinase-1 inhibitor). These results indicate that adenosine formed during renal sympathetic nerve stimulation enhances the postjunctional effects of released norepinephrine via coincident signaling and contributes to renal sympathetic neurotransmission. Likely, the coincident signaling pathway is: phospholipase C → protein kinase C → c-src → phosphatidylinositol 3-kinase → 3-phosphoinositide-dependent protein kinase-1. kidney norepinephrine adenosine receptors A 1 receptor antagonists Copyright © 2012 the American Physiological Society « Previous | Next Article » Table of Contents This Article Published online before print November 2011 , doi: 10.​1152/​ajprenal.​00495.​2011 AJP - Renal Physiol February 2012 vol. 302 no. 4 F466-F476 » Abstract Free Full Text Free to you Full Text (PDF) Free to you Corrigendum All Versions of this Article: ajprenal.00495.2011v1 302/4/F466 most recent Classifications Article Services Email this article to a friend Alert me when this article is cited Alert me if a correction is posted Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Download to citation manager Citing Articles Load citing article information Citing articles via Web of Science Google Scholar Articles by Jackson, E. K. Articles by Mi, Z. PubMed PubMed citation Articles by Jackson, E. K. Articles by Mi, Z. Related Content Load related web page information Current Issue February 2012, 302 (4) Alert me to new issues of AJP - Renal Physiol About the Journal Information for Authors Submit a Manuscript Ethical Policies AuthorChoice PubMed Central Policy Reprints and Permissions Advertising Press Copyright © 2012 the American Physiological Society Print ISSN: 0363-6127 Online ISSN: 1522-1466 var gaJsHost = (("https:" == document.location.protocol) ? "https://ssl." : "http://www."); document.write(unescape("%3Cscript src='" + gaJsHost + "google-analytics.com/ga.js' type='text/javascript'%3E%3C/script%3E")); var pageTracker = _gat._getTracker("UA-2924550-1"); pageTracker._trackPageview();

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