Consequences of eliminating adenosine A(1) receptors in mice
(2003) International Symposium on Adenosine and Adenine Nucleotides, 2003 58(4). p.350-353- Abstract
- 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... (More)
- 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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/309312
- author
- organization
- publishing date
- 2003
- type
- Chapter in Book/Report/Conference proceeding
- publication status
- published
- subject
- keywords
- pain, mice, anxiety, hypoxia, adenosine A(1) receptor gene
- host publication
- Drug Development Research (Proceedings of the Seventh International Symposium on Adenosine and Adenine Nucleotides - Part 1)
- volume
- 58
- issue
- 4
- pages
- 350 - 353
- publisher
- John Wiley & Sons Inc.
- conference name
- International Symposium on Adenosine and Adenine Nucleotides, 2003
- conference location
- Gold Coast, Australia
- conference dates
- 0001-01-02
- external identifiers
-
- wos:000183346600008
- scopus:0038388943
- ISSN
- 1098-2299
- 0272-4391
- DOI
- 10.1002/ddr.10170
- language
- English
- LU publication?
- yes
- id
- 368be195-5924-4481-b0c3-d01904609fea (old id 309312)
- date added to LUP
- 2016-04-01 12:00:24
- date last changed
- 2024-01-08 04:43:30
@inproceedings{368be195-5924-4481-b0c3-d01904609fea,
abstract = {{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.}},
author = {{Fredholm, BB and Halldner, L and Johansson, C and Schulte, G and Lovdahl, C and Thoren, P and Dunwiddie, TV and Masino, SA and Poelchen, W and Diao, LH and Illes, P and Zahniser, NR and Valen, G and Tokuno, S and Sommerschild, H and Gimenez-Llort, L and Fernandez-Teruel, A and Escorihuela, RM and Wiesenfeld-Hallin, Z and Xu, XJ and Hardemark, A and Herlenius, E and Pekny, S and Gebre-Medhin, Samuel and Brown, R and Ollerstam, A and Persson, AEG and Skott, O and Johansson, B}},
booktitle = {{Drug Development Research (Proceedings of the Seventh International Symposium on Adenosine and Adenine Nucleotides - Part 1)}},
issn = {{1098-2299}},
keywords = {{pain; mice; anxiety; hypoxia; adenosine A(1) receptor gene}},
language = {{eng}},
number = {{4}},
pages = {{350--353}},
publisher = {{John Wiley & Sons Inc.}},
title = {{Consequences of eliminating adenosine A(1) receptors in mice}},
url = {{http://dx.doi.org/10.1002/ddr.10170}},
doi = {{10.1002/ddr.10170}},
volume = {{58}},
year = {{2003}},
}