A1 receptor activation decreases fatigue in mammalian slow-twitch skeletal muscle in vitro.
To test the hypothesis that adenosine improves skeletal muscle cell function, 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 contracted in Krebs-Henseleit bicarbonate buffer (27 degrees C, 95% O2 and 5% CO2) for 500 ms at 50 Hz once every 90 s. Soleus fatigued significantly less with adenosine present at concentrations of 10(-8) M and higher than with the Krebs-Henseleit vehicle control. Adenosine significantly improved force generation or delayed fatigue of EDL only with the initial adenosine challenge. To investigate the receptor population involved, we exposed soleus to agonists specific for A1 receptors (N6-cyclopentyladenosine, CPA), or A2 receptors (CGS 21680 hydrochloride, CGS), or A3 receptors (N6-benzyl-5'-N-ethylcarboxamidoadenosine, BNECA). CPA (A1) significantly decreased fatigue compared with the Krebs-Henseleit vehicle control at concentrations of 10(-9) M and higher. Muscles exposed to the A2 and A3 agonists did not differ from a Krebs-Henseleit plus methanol control. Phenylephrine (10(-6) M), an alpha-adrenergic agonist that increases the concentration of inositol triphosphate (IP3), significantly improved developed force in soleus. Neither a permeable cAMP analog, 8-bromo-cAMP (10(-5) M), nor a beta, 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 A1 receptors.
Reading
S A
SA
Department of Human Biology and Nutritional Sciences, University of Guelph, ON, Canada. sreading@uoguelph.ca
Barclay
J K
JK
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D018763:Muscle Fatigue / Q000187:drug effects*; D018656:Muscle Fibers, Fast-Twitch / Q000187:drug effects; D018657:Muscle Fibers, Slow-Twitch / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000187:drug effects*; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000819:agonists*; D014665:Vasodilator Agents / Q000494:pharmacology
D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D014665:Vasodilator Agents; D000241:Adenosine