| Autor: |
Anna Hårdemark, Peter Illes, Björn Johansson, Wolfgang Poelchen, Russell D. Brown, Cecilia Lövdahl, Zsuzsanna Wiesenfeld-Hallin, Catarina Johansson, Bertil B. Fredholm, Rosa M. Escorihuela, Nancy R. Zahniser, Samuel Gebre-Medhin, Anna Ollerstam, Lihong Diao, Shinichi Tokuno, Alberto Fernández-Teruel, Susan A. Masino, Peter Thorén, Eric Herlenius, Thomas V. Dunwiddie, Gunnar Schulte, Ole Skøtt, Linda Halldner, Xiao-Jun Xu, Hilchen Sommerschild, Lydia Giménez-Llort, Milos Pekny, A. Erik G. Persson, Guro Valen |
| Rok vydání: |
2003 |
| Předmět: |
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| Zdroj: |
Drug Development Research. 58:350-353 |
| ISSN: |
0272-4391 |
| Popis: |
The second coding exon of the adenosine A, receptor gene was eliminated by homologous recombination. The phenotype of mice (mixed C57B6/129OlaHsd background) was studied, using siblings from matings of heterozygous mice. Among the offspring the ratio between+/+, +/-and -/-animals was 1:2:1. Over the first half-year-at least-growth and viability were the same in all genotypes. Binding of A(1) ligands was eliminated in-/-mice and halved in+/-mice. Blood pressure was increased in-/-mice and this was paralleled by an increase in plasma renin. Heart rate was unaffected, as was contractility. Furthermore, the response of the perfused heart to ischemia was similar in+/+and -/-hearts. However, remote preconditioning was eliminated in-/-mouse hearts. Tubuloglomerular feedback in the kidney was also lost in-/-mice. The analgesic response to a non-selective adenosing receptor agonist was lost in-/-mice, which also showed hyperalgesia in the tail-flick test. There was a slight hypoactivity in-/-mice, but responses to caffeine were essentially normal. The inhibition of excitatory neurotransmission in hippocampus by adenosine was lost in-/-mice and reduced in+/-mice. Responses to ATP were affected similarly. Hypoxic depression of synaptic transmission was essentially eliminated in hippocampus and hypoxic decrease in spinal respiratory neuron firing was markedly reduced. These results show that adenosine A, receptors play a physiologically important role in the kidney, spinal cord, and hippocampus and that they are critically important in the adaptive responses to hypoxia. (C) 2003 Wiley-Liss, Inc. (Less) |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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