Adenosine A(2) receptors modulate tubuloglomerular feedback.
Adenosine can mediate the tubuloglomerular (TGF) response via activation of A(1) receptors on the afferent arteriole, but both adenosine A(1) and A(2) receptors can regulate preglomerular resistance. We tested the hypothesis that adenosine A(2) receptors offset the effect of A(1) receptors and modulate the TGF. Maximal TGF responses were measured in male Sprague-Dawley rats as changes in proximal stop-flow pressure (DeltaP(SF)) in response to increased perfusion of the loop of Henle (0 to 40 nl/min) with artificial tubular fluid (ATF). The maximal TGF response was studied after 5 min of intratubular perfusion (10 nl/min) with ATF alone, or with ATF plus the A(2A) receptor antagonist (ZM-241385; 10(-7) or 10(-5) mol/l), A(1) receptor antagonist (PSB-36; 10(-8) mol/l), or with a combination of A(1) (PSB-36; 10(-8) mol/l) and A(2A) (ZM-241385; 10(-7) mol/l) antagonists. The maximal TGF response (DeltaP(SF)) with ATF alone was 11.7 +/- 1.0 mmHg. Specific A(2) inhibition (low dose) enhanced the maximal TGF response (15.7 +/- 0.8 mmHg; P < 0.01), whereas a high dose (unspecific inhibition) attenuated the response (5.0 +/- 0.4 mmHg; P < 0.001). A(1) inhibition alone led to a paradoxical TGF response, with an increase in P(SF) of 3.1 +/- 0.5 mmHg (P < 0.05). Simultaneous application of A(1) and A(2) antagonists abolished the TGF response (DeltaP(SF): 0.4 +/- 0.3 mmHg). In conclusion, adenosine A(2) receptors modulate the TGF response by counteracting the effects of adenosine A(1) receptors.
Department of Medicine, Georgetown University Medical Center, Washington, District of Columbia, USA.
Mattias
M
Carlström
Christopher S
CS
Wilcox
William J
WJ
Welch
D000241:Adenosine / Q000378:metabolism*; D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D001160:Arterioles / Q000378:metabolism; D001794:Blood Pressure; D025461:Feedback, Physiological; D007678:Kidney Glomerulus / Q000098:blood supply*; D007684:Kidney Tubules / Q000098:blood supply*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D043682:Receptor, Adenosine A1 / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D012079:Renal Circulation / Q000187:drug effects; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology; D014661:Vasoconstriction; D014664:Vasodilation; D014970:Xanthines / Q000494:pharmacology
C534532:1-butyl-8-(3-noradamantyl)-3-(3-hydroxypropyl)xanthine; D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; D014227:Triazines; D014230:Triazoles; D014970:Xanthines; C097270:ZM 241385; D000241:Adenosine