Hyperalgesia, anxiety, and decreased hypoxic neuroprotection in mice lacking the adenosine A1receptor
| Autor: | Lydia Giménez-Llort, Rosa M. Escorihuela, Linda Halldner, Christer Betsholtz, Zsuzsanna Wiesenfeld-Hallin, Anna Hårdemark, Alberto Fernández-Teruel, Eric Herlenius, Thomas V. Dunwiddie, Xiao-Jun Xu, Susan A. Masino, Wolfgang Poelchen, Bertil B. Fredholm, Björn Johansson |
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| Rok vydání: | 2001 |
| Předmět: |
Male
medicine.medical_specialty Adenosine Anxiety In Vitro Techniques Neurotransmission Hippocampus Neuroprotection Mice Adenosine A1 receptor chemistry.chemical_compound Caffeine Internal medicine medicine Animals Hypoxia Receptor Mice Knockout Multidisciplinary Behavior Animal Receptors Purinergic P1 Biological Sciences Hypoxia (medical) Mice Inbred C57BL Endocrinology chemistry Hyperalgesia Autoradiography medicine.symptom medicine.drug |
| Zdroj: | Proceedings of the National Academy of Sciences. 98:9407-9412 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.161292398 |
| Popis: | Caffeine is believed to act by blocking adenosine A1and A2Areceptors (A1R, A2AR), indicating that some A1receptors are tonically activated. We generated mice with a targeted disruption of the second coding exon of the A1R (A1R−/−). These animals bred and gained weight normally and had a normal heart rate, blood pressure, and body temperature. In most behavioral tests they were similar to A1R+/+mice, but A1R−/−mice showed signs of increased anxiety. Electrophysiological recordings from hippocampal slices revealed that both adenosine-mediated inhibition and theophylline-mediated augmentation of excitatory glutamatergic neurotransmission were abolished in A1R−/−mice. In A1R+/−mice the potency of adenosine was halved, as was the number of A1R. In A1R−/−mice, the analgesic effect of intrathecal adenosine was lost, and thermal hyperalgesia was observed, but the analgesic effect of morphine was intact. The decrease in neuronal activity upon hypoxia was reduced both in hippocampal slices and in brainstem, and functional recovery after hypoxia was attenuated. Thus A1Rs do not play an essential role during development, and although they significantly influence synaptic activity, they play a nonessential role in normal physiology. However, under pathophysiological conditions, including noxious stimulation and oxygen deficiency, they are important. |
| Databáze: | OpenAIRE |
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