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Effects of AMP on core body temperature in A1 adenosine receptor and CD73 knockout mice
Author(s) -
Eisner Christoph,
Kim Soo Mi,
Briggs Josie,
Schnermann Jurgen
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1312-c
Subject(s) - torpor , hypothermia , adenosine , endocrinology , medicine , chemistry , shivering , agonist , adenosine receptor , receptor , thermoregulation , anesthesia
Intraperitoneal injection of 5′‐AMP in conscious mice has been shown to lower core body temperature (CBT) to below 30 °C and to induce a state of torpor for an extended period of time (Zhang et al., Nature 2006). In the current experiments we investigated the role of A1 adenosine receptors (A1AR) in this response. The A1 agonist cyclopentyladenosine (1 mg/kg) reduced CBT to a nadir of 23.3 °C ± 0.3 at 160 min (n=5). 5′‐AMP induced dose‐dependent non‐shivering hypothermia and torpor at doses between 55 and 550 mg/kg. At the highest dose, AMP reduced CBT by 10.8 °C ± 0.6 at 80 min in wild type mice (WT; n=5) while CBT fell by only 6.6 °C ± 0.54 in A1AR−/− mice (n=5; p<0.001). The time of CBT to return to normal was about 4 hrs in WT and 2 hrs in A1AR−/−. As measured by telemetry, the time course of the hypothermic state was paralleled by marked blood pressure and heart rate reductions (to a nadir of 40 mm Hg and 200 bpm in WT, and 60 mm Hg and 400 bpm in A1AR−/−). At 550 mg/kg, locomotor activity was completely suppressed between 45 and 210 min in WT, and between 60 and 120 min in A1AR−/−. In contrast to A1AR−/−, AMP‐induced hypothermia was not significantly different from WT in CD73−/− mice (−11.1 °C ± 0.6; n=5). In summary: 1. AMP induces dose‐dependent non‐shivering and long‐lasting hypothermia in conscious mice; 2. hypothermia is accompanied by blood pressure and heart rate reductions, and immobility; 3. all of these effects are smaller in A1AR−/− than WT or CD73−/− mice. We conclude that AMP‐induced hypothermia is partly mediated by A1AR, and that adenosine levels at the central or peripheral site of action can be maintained in the absence of ecto‐5′‐nucleotidase.