Faculty Collaboration Database

Hypothermia in mouse is caused by adenosine A₁ and A₃ receptor agonists and AMP via three distinct mechanisms. Neuropharmacology 2017 Mar 01;114:101-113

Date

12/05/2016

Pubmed ID

27914963

Pubmed Central ID

PMC5183552

DOI

10.1016/j.neuropharm.2016.11.026

Scopus ID

2-s2.0-85002410442 (requires institutional sign-in at Scopus site)   53 Citations

Abstract

Small mammals have the ability to enter torpor, a hypothermic, hypometabolic state, allowing impressive energy conservation. Administration of adenosine or adenosine 5'-monophosphate (AMP) can trigger a hypothermic, torpor-like state. We investigated the mechanisms for hypothermia using telemetric monitoring of body temperature in wild type and receptor knock out (Adora1^-/-, Adora3^-/-) mice. Confirming prior data, stimulation of the A₃ adenosine receptor (AR) induced hypothermia via peripheral mast cell degranulation, histamine release, and activation of central histamine H₁ receptors. In contrast, A₁AR agonists and AMP both acted centrally to cause hypothermia. Commonly used, selective A₁AR agonists, including N⁶-cyclopentyladenosine (CPA), N⁶-cyclohexyladenosine (CHA), and MRS5474, caused hypothermia via both A₁AR and A₃AR when given intraperitoneally. Intracerebroventricular dosing, low peripheral doses of Cl-ENBA [(±)-5'-chloro-5'-deoxy-N⁶-endo-norbornyladenosine], or using Adora3^-/- mice allowed selective stimulation of A₁AR. AMP-stimulated hypothermia can occur independently of A₁AR, A₃AR, and mast cells. A₁AR and A₃AR agonists and AMP cause regulated hypothermia that was characterized by a drop in total energy expenditure, physical inactivity, and preference for cooler environmental temperatures, indicating a reduced body temperature set point. Neither A₁AR nor A₃AR was required for fasting-induced torpor. A₁AR and A₃AR agonists and AMP trigger regulated hypothermia via three distinct mechanisms.

Author List

Carlin JL, Jain S, Gizewski E, Wan TC, Tosh DK, Xiao C, Auchampach JA, Jacobson KA, Gavrilova O, Reitman ML

Authors

John A. Auchampach PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Tina C. Wan PhD Research Scientist II in the Pediatrics department at Medical College of Wisconsin

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

Adenosine
Adenosine A1 Receptor Agonists
Adenosine A3 Receptor Agonists
Adenosine Monophosphate
Animals
Brain
Fever
Histamine
Injections, Intraventricular
Male
Mast Cells
Mice
Mice, Inbred C57BL
Receptor, Adenosine A1
Receptor, Adenosine A3
Receptors, Histamine H1
Torpor