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Role of β‐adrenoceptors in glucose uptake in astrocytes using β‐adrenoceptor knockout mice
Author(s) -
Catus Stephanie L,
Gibbs Marie E,
Sato Masaaki,
Summers Roger J,
Hutchinson Dana S
Publication year - 2011
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2010.01153.x
Subject(s) - endocrinology , medicine , stimulation , knockout mouse , receptor , adrenergic receptor , biology , radioligand , astrocyte , signal transduction , microbiology and biotechnology , central nervous system
BACKGROUND AND PURPOSE β 1 ‐, β 2 ‐ and β 3 ‐adrenoceptors determined by functional, binding and reverse transcription polymerase chain reaction (RT‐PCR) studies are present in chick astrocytes and activation of β 2 ‐ or β 3 ‐adrenoceptors increase glucose uptake. The aims of the present study are to identify which β‐adrenoceptor subtypes are present in mouse astrocytes, the signal transduction mechanisms involved and whether β‐adrenoceptor stimulation regulates glucose uptake. EXPERIMENTAL APPROACH Astrocytes were prepared from four mouse strains: FVB/N, DBA/1 crossed with C57BL/6J, β 3 ‐adrenoceptor knockout and β 1 β 2 ‐adrenoceptor knockout mice. RT‐PCR and radioligand binding studies were used to determine β‐adrenoceptor expression. Glucose uptake and cAMP were assayed to elucidate the signalling pathways involved. KEY RESULTS mRNAs for all three β‐adrenoceptors were identified in astrocytes from wild‐type mice. Radioligand binding studies identified that β 1 ‐ and β 3 ‐adrenoceptors were predominant. cAMP studies showed that β 1 ‐ and β 2 ‐adrenoceptors coupled to G s whereas β 3 ‐adrenoceptors coupled to both G s and G i . However, activation of any of the three β‐adrenoceptors increased glucose uptake in mouse astrocytes. Interestingly, there was no functional compensation for receptor subtype loss in knockout animals. CONCLUSIONS AND IMPLICATIONS This study demonstrates that although β 1 ‐adrenoceptors are the predominant β‐adrenoceptor in mouse astrocytes and are primarily responsible for cAMP production in response to β‐adrenoceptor stimulation, β 3 ‐adrenoceptors are also present in mouse astrocytes and activation of β 2 ‐ and β 3 ‐adrenoceptors increases glucose uptake in mouse astrocytes.