Activation of adenosine A(2A) or A(2B) receptors causes hypothermia in mice

作者：Carlin Jesse Lea; Jain Shalini; Duroux Romain; Suresh R Rama; Xiao Cuiying; Auchampach John A; Jacobson Kenneth A; Gavrilova Oksana; Reitman Marc L^*

来源：Neuropharmacology, 2018, 139: 268-278.

DOI：10.1016/j.neuropharm.2018.02.035

• Hypothermia
• Adenosine
• A(2A)AR
• A(2B)AR
• Preoptic area
• Paraventricular hypothalamus

Extracellular adenosine is a danger/injury signal that initiates protective physiology, such as hypothermia. Adenosine has been shown to trigger hypothermia via agonism at A(1) and A(3) adenosine receptors (A(1)AR, A(3)AR). Here, we find that adenosine continues to elicit hypothermia in mice null for A(1A)R and A(3A)R and investigated the effect of agonism at A(2A)AR or A(2B)AR. The poorly brain penetrant A(2A)AR agonists CGS-21680 and PSB-0777 caused hypothermia, which was not seen in mice lacking A(2A)AR. MRS7352, a likely non-brain penetrant A(2A)AR antagonist, inhibited PSB-0777 hypothermia. While vasodilation is probably a contributory mechanism, A(2A)AR agonism also caused hypometabolism, indicating that vasodilation is not the sole mechanism. The A(2B)AR agonist BAY60-6583 elicited hypothermia, which was lost in mice null for A(2B)AR. Low intracerebroventricular doses of BAY60-6583 also caused hypothermia, indicating a brain site of action, with neuronal activation in the preoptic area and paraventricular nucleus of the hypothalamus. Thus, agonism at any one of the canonical adenosine receptors, A(1)AR, A(2A)AR, A(2B)AR, or A(3A)R, can cause hypothermia. This four-fold redundancy in adenosine-mediated initiation of hypothermia may reflect the centrality of hypothermia as a protective response. Published by Elsevier Ltd.

• 出版日期2018-9-1
• 单位NIH