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Published on: June 27, 2015
Adenosine A(2) receptors modulate tubuloglomerular feedback
Mattias Carlström1, Christopher S Wilcox, William J Welch
1Department of Medicine, Georgetown University Medical Center, Washington, District of Columbia, USA.
Adenosine A(2) receptors modulate the tubuloglomerular feedback (TGF) response by counteracting adenosine A(1) receptor effects. This study investigated adenosine receptor roles in regulating kidney function and preglomerular resistance.
Area of Science:
- Nephrology
- Renal Physiology
- Pharmacology
Background:
- Adenosine mediates the tubuloglomerular feedback (TGF) response via A(1) receptors on the afferent arteriole.
- Both adenosine A(1) and A(2) receptors are known to regulate preglomerular resistance.
Purpose of the Study:
- To test the hypothesis that adenosine A(2) receptors offset the effects of A(1) receptors.
- To investigate the modulatory role of adenosine A(2) receptors on the TGF response.
Main Methods:
- Maximal TGF responses were measured in Sprague-Dawley rats by assessing changes in proximal stop-flow pressure (DeltaP(SF)).
- Responses were evaluated during loop of Henle perfusion with artificial tubular fluid (ATF) alone or with A(1) and/or A(2A) receptor antagonists (PSB-36 and ZM-241385).
Main Results:
- Specific A(2) receptor inhibition (low dose) enhanced the maximal TGF response (15.7 mmHg vs. 11.7 mmHg baseline).
- High-dose A(2) inhibition attenuated the TGF response (5.0 mmHg), while A(1) inhibition caused a paradoxical increase (3.1 mmHg).
- Simultaneous A(1) and A(2) antagonism abolished the TGF response (0.4 mmHg).
Conclusions:
- Adenosine A(2) receptors play a significant role in modulating the TGF response.
- These A(2) receptors counteract the effects mediated by adenosine A(1) receptors within the renal vasculature.
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