Role of β-adrenoceptors in glucose uptake in astrocytes using β-adrenoceptor knockout mice.
OBJECTIVE
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.


METHODS
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.


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
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.
Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
Stephanie L
SL
Catus
Marie E
ME
Gibbs
Masaaki
M
Sato
Roger J
RJ
Summers
Dana S
DS
Hutchinson
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D011869:Radioligand Assay; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000378:metabolism*; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012333:RNA, Messenger; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D022702:Receptors, Adrenergic, beta-3; D000242:Cyclic AMP; D005947:Glucose