A(1) receptor activation decreases fatigue in mammalian slow-twitch skeletal muscle in vitro

To test the hypothesis that adenosine improves skeletal muscle cell functio n, we exposed curarized mouse soleus and extensor digitorum longus (EDL) to a range of concentrations of adenosine (10(-9) M to 10(-5) M). Muscles con tracted in Krebs-Henseleit bicarbonate buffer (27 degreesC, 95% O-2 and 5% CO2) for 500 ms at 50 Hz once every 90 s. Soleus fatigued significantly les s with adenosine present at concentrations of 10(-8) M and higher than with the Krebs-Henseleit vehicle control. Adenosine significantly improved forc e generation or delayed fatigue of EDL only with the initial adenosine chal lenge. To investigate the receptor population involved, we exposed soleus t o agonists specific for A(1) receptors (N-6-cyclopentyladenosine, CPA), or A(2) receptors (CGS 21680 hydrochloride, CGS), or A(3) receptors (N-6-benzy l-5'-N-ethylcarboxamidoadenosine, BNECA). CPA (A(1)) significantly decrease d fatigue compared with the Krebs-Henseleit vehicle control at concentratio ns of 10(-9) M and higher. Muscles exposed to the A(2) and A(3) agonists di d not differ from a Krebs-Henseleit plus methanol control. Phenylephrine (1 0(-6) M), an alpha-adrenergic agonist that increases the concentration of i nositol triphosphate (IP3), significantly improved developed force in soleu s. Neither a permeable cAMP analog, 8-bromo-cAMP (10(-5) M), nor a beta(1) agonist, isoproterenol (10(-6) M), had an effect on force generation in the soleus when compared with a saline control. Thus adenosine slowed fatigue in slow-twitch skeletal muscle through A(1) receptors.