Role of beta-adrenoceptors in glucose uptake in astrocytes using beta-adrenoceptor knockout mice

Stephanie Lee Catus, Marie E Gibbs, Masaaki Sato, Roger James Summers, Dana Sabine Hutchinson

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33 Citations (Scopus)

Abstract

Background and purpose: beta(1) -, beta(2) - and beta(3) -adrenoceptors determined by functional, binding and reverse transcription polymerase chain reaction (RT-PCR) studies are present in chick astrocytes and activation of beta(2) - or beta(3) -adrenoceptors increase glucose uptake. The aims of the present study are to identify which beta-adrenoceptor subtypes are present in mouse astrocytes, the signal transduction mechanisms involved and whether beta-adrenoceptor stimulation regulates glucose uptake. Experimental approach: Primary astrocytes were prepared from 4 mouse strains: FVB/N (FVB), DBA/1 crossed with C57BL/6J (DBAxC57), beta(3) -adrenoceptor knock out (beta(3) KO) and beta(1) beta(2) -adrenoceptor knock out (beta(1) beta(2) KO) mice. RT-PCR and radioligand binding studies were used to determine beta-adrenoceptor expression. Glucose uptake and cAMP were assayed to elucidate the signalling pathways involved. Key results: mRNAs for all three beta-adrenoceptors were identified in astrocytes from wild-type mice. Radioligand binding studies identified that beta(1) - and beta(3) -adrenoceptors were predominant. cAMP studies showed that beta(1) - and beta(2) -adrenoceptors coupled to G(s) whereas beta(3) -adrenoceptors coupled to both G(s) and G(i) . However activation of any of the three beta-adrenoceptors increased glucose uptake in mouse astrocytes. Interestingly, there was no functional compensation for receptor subtype loss in KO animals. Conclusions and implications: This study demonstrates that although beta(1) -adrenoceptors are the predominant beta-adrenoceptor in mouse astrocytes and are primarily responsible for cAMP production in response to beta-adrenoceptor stimulation, beta(3) -adrenoceptors are also present in mouse astrocytes and activation of beta(2) - and beta(3) -adrenoceptors increases glucose uptake in mouse astrocytes.
Original languageEnglish
Pages (from-to)1700 - 1715
Number of pages16
JournalBritish Journal of Pharmacology
Volume162
Issue number8
DOIs
Publication statusPublished - 2011

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