![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
CELLULAR AND MOLECULAR
2-Adrenoceptor Agonist Prodrug BRL-47672 on Cardiovascular Function, Skeletal Muscle Myosin Heavy Chain, and MyoD Expression in the Rat
Centre for Integrated Systems Biology and Medicine, Queens Medical Centre, University of Nottingham, Nottingham, United Kingdom (S.W.J., D.J.B., S.M.G., T.B., P.L.G.); and Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (J.A.T.)
The intracellular mechanisms that regulate changes in postnatal myosin heavy chain (MHC) expression are not well established. The major objective of this study was to examine the acute and chronic effects of administration of BRL-47672, the prodrug of the 
2-adrenoceptor agonist clenbuterol on MHC and MyoD transcription factor expression to determine whether or not changes in MHC composition are preceded by changes in MyoD protein expression. To assess to what extent the use of BRL-47672 minimized cardiovascular effects, its hemodynamic actions were compared with those of clenbuterol. The effect of BRL-47672 on heart rate, mean arterial blood pressure, and hindquarters vascular conductance was significantly less than that of clenbuterol after a single i.p. injection (250 µg kg-1 body mass). In the main study, 4-week old rats were given BRL-47672 (900 µg kg-1 body mass) or an equivalent volume of saline (control) daily for 1, 28, or 56 days. Soleus muscle (SOL) was excised and MHC and MyoD expression analyzed. After 4 weeks, SOL from the BRL-47672-treated animals had significantly faster MHC composition (49 ± 2% MHCIIA) compared with those from the control animal (39 ± 3% MHCIIA, P < 0.05). MyoD expression increased by 40% after 1 day of BRL-47672 administration (P < 0.05) before a change in MHC composition. In conclusion, these data suggest that increased expression of fast-type MHCIIA expression in rat SOL induced by BRL-47672 administration is preceded by changes in the level of MyoD transcription factor expression.
Address correspondence to: Prof. Paul L. Greenhaff, Centre for Integrated Systems Biology and Medicine, Queens Medical Centre, University of Nottingham, Nottingham, NG7 2UH, UK. E-mail: paul.greenhaff{at}nottingham.ac.uk
This article has been cited by other articles:
|
|
 |
|
  G. S. Lynch and J. G. Ryall Role of {beta}-Adrenoceptor Signaling in Skeletal Muscle: Implications for Muscle Wasting and Disease Physiol Rev, April 1, 2008; 88(2): 729 - 767. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. G. Burniston, L.-B. Tan, and D. F. Goldspink Relative myotoxic and haemodynamic effects of the {beta}-agonists fenoterol and clenbuterol measured in conscious unrestrained rats Exp Physiol, November 1, 2006; 91(6): 1041 - 1049. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Baker, D. Constantin-Teodosiu, S. W. Jones, J. A. Timmons, and P. L. Greenhaff Chronic Treatment with the beta2-Adrenoceptor Agonist Prodrug BRL-47672 Impairs Rat Skeletal Muscle Function by Inducing a Comprehensive Shift to a Faster Muscle Phenotype J. Pharmacol. Exp. Ther., October 1, 2006; 319(1): 439 - 446. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Baker, A. C. Betik, D. J. Krause, and R. T. Hepple No decline in skeletal muscle oxidative capacity with aging in long-term calorically restricted rats: effects are independent of mitochondrial DNA integrity. J. Gerontol. A Biol. Sci. Med. Sci., July 1, 2006; 61(7): 675 - 684. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. G. McDaneld, K. Hannon, and D. E. Moody Ankyrin repeat and SOCS box protein 15 regulates protein synthesis in skeletal muscle Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2006; 290(6): R1672 - R1682. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
