Different effects of enantiomers of beta2-adrenergic agonist on muscle and bone.

When (-)-(R)- and (+)-(S)-enantiomers of 2-adrenergic receptor (β2-AR) agonist tulobuterol （each 10）mg/kg) was subcutaneously injected into female young rats once a day for 4 weeks，the effects of each enantiomer on the muscle and bone examined. the (-)-(R)-enantiomerbut not (+)-(S)-enantiomer, significantly increased the body weight and decreased fat，compared with vehicle control. Particularly，the (R)-enantiomer not only increased the heart muscle and skeletal muscle but shifted the musclelactate dehydrogenase (LDH) isoenzyme from the H-type to M-type and also myosin heavy chain （HMC）isoform pattern from slow type to fast type. On the other hand，the (S)-enantiomer decreased the bone mineral densityaccompanied with increase in urinary deoxypyridinoline excretion.体外，osteoclast-like cell formation were generated in co-culture，mouse bone marrow cells (BMC) and ST2-T cells preparations for 7 days，treated with (S)-enantiomer more than with (R)-enantiomer. Moreover，inhibited by selective β2-AR inhibitor butoxamine and non-selective β-AR inhibitorpropranolol. The effects of (R)-enantiomer of β2-AR agonist should be convenient for athletes andexercisers,but the (S) enantiomer might influence the bone growth and increase the risk of bone fracture inyoung users,in particular when used illegal dosage as doping. This study is the first report indicating thedifferent activities of (R)- and (S)-enantiomers of β -AR agonist on the muscle and bone. We need tocarry out“racemiswitch”to develop drugs consisting useful active enantiomer。

When (-)-(R)- and (+)-(S)-enantiomers of ・2-adrenergic receptor (β2-AR) agonist tulobuterol (each 10 mg/kg) was subcutaneously injected into female young rats once a day for 4 weeks, the effects of each enantiomer on the muscle and bone were examined. The (-)-(R)-enantiomer, but not (+)-(S)-enantiomer, significantly increased the body weight and decreased fat, compared with vehicle control. Particularly, the (R)-enantiomer not only increased the heart muscle and skeletal muscle but shifted the muscle lactate dehydrogenase (LDH) isoenzyme from the H-type to M-type and also myosin heavy chain (HMC) isoform pattern from slow type to fast type. On the other hand, the (S)-enantiomer decreased the bone mineral density, accompanied with increase in urinary deoxypyridinoline excretion. In vitro, osteoclast-like cell formation were generated in co-culture, mouse bone marrow cells (BMC) and ST2-T cells preparations for 7 days, treated with (S)-enantiomer more than with (R)-enantiomer. Moreover, it was inhibited by selective β2-AR inhibitor butoxamine and non-selective β-AR inhibitor propranolol. The effects of (R)-enantiomer of β2-AR agonist should be convenient for athletes and exercisers, but the (S)-enantiomer might influence the bone growth and increase the risk of bone fracture in young users, in particular when used illegal dosage as doping. This study is the first report indicating the different activities of (R)- and (S)-enantiomers of β2-AR agonist on the muscle and bone. We need to carry out “racemiswitch” to develop drugs consisting useful active enantiomer.