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Consequences of eliminating adenosine A(1) receptors in mice

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Author

  • BB Fredholm
  • L Halldner
  • C Johansson
  • G Schulte
  • C Lovdahl
  • P Thoren
  • TV Dunwiddie
  • SA Masino
  • W Poelchen
  • LH Diao
  • P Illes
  • NR Zahniser
  • G Valen
  • S Tokuno
  • H Sommerschild
  • L Gimenez-Llort
  • A Fernandez-Teruel
  • RM Escorihuela
  • Z Wiesenfeld-Hallin
  • XJ Xu
  • A Hardemark
  • E Herlenius
  • S Pekny
  • Samuel Gebre-Medhin
  • R Brown
  • A Ollerstam
  • AEG Persson
  • O Skott
  • B Johansson
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Summary, in English

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.

Publishing year

2003

Language

English

Pages

350-353

Publication/Series

Drug Development Research (Proceedings of the Seventh International Symposium on Adenosine and Adenine Nucleotides - Part 1)

Volume

58

Issue

4

Document type

Conference paper

Publisher

John Wiley & Sons Inc.

Topic

  • Medical Genetics

Keywords

  • pain
  • mice
  • anxiety
  • hypoxia
  • adenosine A(1) receptor gene

Conference name

International Symposium on Adenosine and Adenine Nucleotides, 2003

Conference date

0001-01-02

Conference place

Gold Coast, Australia

Status

Published

ISBN/ISSN/Other

  • ISSN: 0272-4391
  • ISSN: 1098-2299