Effect of adenosine A1 analogue on tubuloglomerular feedback mechanism.
To evaluate further the role of adenosine in the transmission of tubuloglomerular feedback signals, we studied the effects of an adenosine receptor antagonist and an adenosine A1-receptor agonist on feedback-mediated changes in stop-flow pressure (SFP). In orthograde perfusion experiments conducted in anesthetized rats, systemic administration of the adenosine receptor blocker 1,3-dipropyl-8-sulfophenylxanthine (PSPX) did not inhibit feedback responses. Control SFP feedback responses averaged 9.7 +/- 0.65 before and 8.6 +/- 0.55 mmHg during systemic infusion of the receptor blocker. In retrograde perfusion experiments, intratubular administration of the A1 agonist (360 nM) N6-cyclopentyladenosine (CPA), added to a hypotonic solution, markedly enhanced feedback responses. This effect was completely prevented by coinfusion of PSPX. Addition of 10 mM of the antagonist to the CPA-containing solution attenuated SFP feedback responses to less than 1 mmHg (delta = 0.44 +/- 0.50). Furthermore, PSPX also inhibited feedback responses obtained with an isotonic solution alone. Furosemide, which has been shown to block normal SFP responses obtained with isotonic solutions, failed to block CPA-induced decreases in SFP. These data demonstrate that intraluminal administration of an adenosine A1 analogue causes feedback-mediated decreases in SFP and therefore support a role for adenosine receptors in the signal transmission pathway.
Department of Physiology and Biophysics, University of Alabama, Birmingham 35294.
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Franco
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Bell
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Navar
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D005246:Feedback; D006982:Hypertonic Solutions; D007038:Hypotonic Solutions; D007678:Kidney Glomerulus / Q000187:drug effects / Q000502:physiology*; D007684:Kidney Tubules / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D011983:Receptors, Purinergic / Q000187:drug effects / Q000502:physiology*; D014970:Xanthines / Q000494:pharmacology*
D006982:Hypertonic Solutions; D007038:Hypotonic Solutions; D011983:Receptors, Purinergic; D014970:Xanthines; C048599:N(6)-cyclopentyladenosine; C053896:1,3-dipropyl-8-(4-sulfophenyl)xanthine; D000241:Adenosine