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Activation of neuronal adenosine A1 receptors causes hypothermia through central and peripheral mechanisms.
Province, Haley S; Xiao, Cuiying; Mogul, Allison S; Sahoo, Ankita; Jacobson, Kenneth A; Piñol, Ramón A; Gavrilova, Oksana; Reitman, Marc L.
Afiliação
  • Province HS; Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, United States of America.
  • Xiao C; Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, United States of America.
  • Mogul AS; Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, United States of America.
  • Sahoo A; Mouse Metabolism Core, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, United States of America.
  • Jacobson KA; Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, United States of America.
  • Piñol RA; Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, United States of America.
  • Gavrilova O; Mouse Metabolism Core, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, United States of America.
  • Reitman ML; Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, United States of America.
PLoS One ; 15(12): e0243986, 2020.
Article em En | MEDLINE | ID: mdl-33326493
ABSTRACT
Extracellular adenosine, a danger signal, can cause hypothermia. We generated mice lacking neuronal adenosine A1 receptors (A1AR, encoded by the Adora1 gene) to examine the contribution of these receptors to hypothermia. Intracerebroventricular injection of the selective A1AR agonist (Cl-ENBA, 5'-chloro-5'-deoxy-N6-endo-norbornyladenosine) produced hypothermia, which was reduced in mice with deletion of A1AR in neurons. A non-brain penetrant A1AR agonist [SPA, N6-(p-sulfophenyl) adenosine] also caused hypothermia, in wild type but not mice lacking neuronal A1AR, suggesting that peripheral neuronal A1AR can also cause hypothermia. Mice expressing Cre recombinase from the Adora1 locus were generated to investigate the role of specific cell populations in body temperature regulation. Chemogenetic activation of Adora1-Cre-expressing cells in the preoptic area did not change body temperature. In contrast, activation of Adora1-Cre-expressing dorsomedial hypothalamus cells increased core body temperature, concordant with agonism at the endogenous inhibitory A1AR causing hypothermia. These results suggest that A1AR agonism causes hypothermia via two distinct mechanisms brain neuronal A1AR and A1AR on neurons outside the blood-brain barrier. The variety of mechanisms that adenosine can use to induce hypothermia underscores the importance of hypothermia in the mouse response to major metabolic stress or injury.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Receptor A1 de Adenosina / Hipotermia Tipo de estudo: Etiology_studies Limite: Animals Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Receptor A1 de Adenosina / Hipotermia Tipo de estudo: Etiology_studies Limite: Animals Idioma: En Ano de publicação: 2020 Tipo de documento: Article