Mediation of tubuloglomerular feedback by adenosine: evidence from mice lacking adenosine 1 receptors
| Autor: | Linda C. Samuelson, Jurgen Schnermann, Josie P. Briggs, Tianxin Yang, Alex Paliege, Thom Saunders, Daqing Sun, Yuning Huang |
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| Rok vydání: | 2001 |
| Předmět: |
Male
medicine.medical_specialty Adenosine Genotype Nephron Biology Sodium Chloride Feedback Renal Circulation Electrolytes Mice Oxygen Consumption Internal medicine medicine Loop of Henle Animals RNA Messenger Receptor Tubuloglomerular feedback Mice Knockout Multidisciplinary Reverse Transcriptase Polymerase Chain Reaction Hemodynamics Receptors Purinergic P1 Juxtaglomerular apparatus Biological Sciences Adenosine receptor Juxtaglomerular Apparatus Mice Inbred C57BL Arterioles medicine.anatomical_structure Endocrinology Kidney Tubules Vasoconstriction Models Animal Macula densa Female Energy Metabolism medicine.drug Glomerular Filtration Rate |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 98(17) |
| ISSN: | 0027-8424 |
| Popis: | Adenosine is a determinant of metabolic control of organ function increasing oxygen supply through the A2 class of adenosine receptors and reducing oxygen demand through A1 adenosine receptors (A1AR). In the kidney, activation of A1AR in afferent glomerular arterioles has been suggested to contribute to tubuloglomerular feedback (TGF), the vasoconstriction elicited by elevations in [NaCl] in the macula densa region of the nephron. To further elucidate the role of A1AR in TGF, we have generated mice in which the entire A1AR coding sequence was deleted by homologous recombination. Homozygous A1AR mutants that do not express A1AR mRNA transcripts and do not respond to A1AR agonists are viable and without gross anatomical abnormalities. Plasma and urinary electrolytes were not different between genotypes. Likewise, arterial blood pressure, heart rates, and glomerular filtration rates were indistinguishable between A1AR +/+ , A1AR +/− , and A1AR −/− mice. TGF responses to an increase in loop of Henle flow rate from 0 to 30 nl/min, whether determined as change of stop flow pressure or early proximal flow rate, were completely abolished in A1AR −/− mice (stop flow pressure response, −6.8 ± 0.55 mmHg and −0.4 ± 0.2 in A1AR +/+ and A1AR −/− mice; early proximal flow rate response, −3.4 ± 0.4 nl/min and +0.02 ± 0.3 nl/min in A1AR +/+ and A1AR −/− mice). Absence of TGF responses in A1AR-deficient mice suggests that adenosine is a required constituent of the juxtaglomerular signaling pathway. A1AR null mutant mice are a promising tool to study the functional role of A1AR in different target tissues. |
| Databáze: | OpenAIRE |
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