Faculty Collaboration Database

Activation of adenosine A_2A or A_2B receptors causes hypothermia in mice. Neuropharmacology 2018 Sep 01;139:268-278

Date

03/20/2018

Pubmed ID

29548686

Pubmed Central ID

PMC6067974

DOI

10.1016/j.neuropharm.2018.02.035

Scopus ID

2-s2.0-85043451256 (requires institutional sign-in at Scopus site)   17 Citations

Abstract

Extracellular adenosine is a danger/injury signal that initiates protective physiology, such as hypothermia. Adenosine has been shown to trigger hypothermia via agonism at A₁ and A₃ adenosine receptors (A₁AR, A₃AR). Here, we find that adenosine continues to elicit hypothermia in mice null for A₁AR and A₃AR and investigated the effect of agonism at A_2AAR or A_2BAR. The poorly brain penetrant A_2AAR agonists CGS-21680 and PSB-0777 caused hypothermia, which was not seen in mice lacking A_2AAR. MRS7352, a likely non-brain penetrant A_2AAR antagonist, inhibited PSB-0777 hypothermia. While vasodilation is probably a contributory mechanism, A_2AAR agonism also caused hypometabolism, indicating that vasodilation is not the sole mechanism. The A_2BAR agonist BAY60-6583 elicited hypothermia, which was lost in mice null for A_2BAR. 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, A₁AR, A_2AAR, A_2BAR, or A₃AR, can cause hypothermia. This four-fold redundancy in adenosine-mediated initiation of hypothermia may reflect the centrality of hypothermia as a protective response.

Author List

Carlin JL, Jain S, Duroux R, Suresh RR, Xiao C, Auchampach JA, Jacobson KA, Gavrilova O, Reitman ML

Author

John A. Auchampach PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenosine A2 Receptor Agonists
Adenosine A2 Receptor Antagonists
Animals
Energy Metabolism
Hypothermia
Male
Mice, Inbred C57BL
Mice, Knockout
Motor Activity
Neurons
Paraventricular Hypothalamic Nucleus
Preoptic Area
Receptor, Adenosine A2A
Receptor, Adenosine A2B