Characterization of the β‐adrenoceptor subtype involved in mediation of glucose transport in L6 cells

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Abstract
The receptor that mediates the increase in glucose transport (GT) in response to β‐adrenoceptor (β‐AR) agonists was characterized in the rat skeletal muscle cell line L6, using the 2‐deoxy‐[3H]‐D‐glucose assay. The β3‐AR agonist BRL37344 (pEC50=6.89±0.21), the β‐AR agonist isoprenaline (pEC50=8.99±0.24) and the β2‐AR agonist zinterol (pEC50=9.74±0.15) increased GT as did insulin (pEC50=6.93±0.15). The highly selective β3‐AR agonist CL316243 only weakly stimulated GT. The pKB values calculated from the shift of the pEC50 values of the agonists in the presence of the β1‐AR selective antagonist CGP 20712A or the β3‐AR selective antagonist SR 59230A were not indicative of activation of β1‐ or β3‐ARs. Only (−)‐propranolol and the β2‐AR selective antagonist ICI 118551 caused marked rightward shifts of CR curves to isoprenaline (pKB=10.2±0.2 and 9.6±0.3), zinterol (pKB=9.0±0.1 and 9.4±0.3) and BRL 37344 (pKB=9.4±0.3 and 8.4±.2), indicating participation of β2‐ARs. The pharmacological analysis was supported by reverse transcription and polymerase chain reaction analysis of L6 mRNA, which showed high levels of expression of β2‐AR but not β1‐ or β3‐AR in these cells. Forskolin and dibutyryl cyclic AMP produced negligible increases in GT while the phosphatidylinositol‐3 kinase inhibitor, wortmannin, significantly decreased both insulin‐ and zinterol‐stimulated GT, suggesting a possible interaction between the insulin and β2‐AR pathways. This study demonstrates that β2‐ARs mediate the increase in GT in L6 cells to β‐AR agonists, including the β3‐AR selective agonist BRL 37344. This effect does not appear to be directly related to increases in cyclic AMP but requires P13K. British Journal of Pharmacology (2002) 137, 9–18. doi:10.1038/sj.bjp.0704845

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