β2- and β3-Adrenoceptors activate glucose uptake in chick astrocytes by distinct mechanisms: A mechanism for memory enhancement?

Abstract

Isoprenaline, acting at β-adrenoceptors (ARs), enhances memory formation in single trial discriminated avoidance learning in day-old chicks by mechanisms involving alterations in glucose and glycogen metabolism. Earlier studies of memory consolidation in chicks indicated that β3-ARs enhanced memory by increasing glucose uptake, whereas β2-ARs enhance memory by increasing glycogenolysis. This study examines the ability of β-ARs to increase glucose uptake in chick forebrain astrocytes. The β-AR agonist isoprenaline increased glucose uptake in a concentration-dependent manner, as did insulin. Glucose uptake was increased by the β2-AR agonist zinterol and the β3-AR agonist CL316243, but not by the β1-AR agonist RO363. In chick astrocytes, reverse transcription-polymerase chain reaction studies showed that β1-, β2-, and β3-AR mRNA were present, whereas radioligand-binding studies showed the presence of only β2- and β3-ARs. β-AR or insulin-mediated glucose uptake was inhibited by phosphatidylinositol-3 kinase and protein kinase C inhibitors, suggesting a possible interaction between the β-AR and insulin pathways. However β2- and β3-ARs increase glucose uptake by two different mechanisms: β2-ARs via a Gs-cAMP-protein kinase A-dependent pathway, while β3-ARs via interactions with Gi. These results indicate that activation of β2- and β3-ARs causes glucose uptake in chick astrocytes by distinct mechanisms, which may be relevant for memory enhancement. © 2007 The Authors.