Involvement of adenosine in depression of synaptic transmission during hypercapnia in isolated spinal cord of neonatal rats.
Adenosine is one of the most important neuromodulators in the CNS, both under physiological and pathological conditions. In the isolated spinal cord of the neonatal rat in vitro, acute hypercapnic acidosis (20% CO2, pH 6.7) reversibly depressed electrically evoked spinal reflex potentials. This depression was partially reversed by 8-cyclopentlyl-1,3-dimethylxanthine (CPT), a selective A1 adenosine receptor antagonist. Isohydric hypercapnia (20% CO2, pH 7.3), but not isocapnic acidosis (5% CO2, pH 6.7), depressed the reflex potentials, which were also reversed by CPT. An ecto-5'-nucleotidase inhibitor did not affect the hypercapnic acidosis-evoked depression. An inhibitor of adenosine kinase, but not deaminase, mimicked the inhibitory effect of hypercapnic acidosis on the spinal reflex potentials. Accumulation of extracellular adenosine and inhibition of adenosine kinase activity were caused by hypercapnic acidosis and isohydric hypercapnia, but not isohydric acidosis. These results indicate that the activation of adenosine A1 receptors is involved in the hypercapnia-evoked depression of reflex potentials in the isolated spinal cord of the neonatal rat. The inhibition of adenosine kinase activity is suggested to cause the accumulation of extracellular adenosine during hypercapnia.
Otsuguro
Ken-ichi
K
Laboratory of Pharmacology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan. otsuguro@vetmed.hokudai.ac.jp
Yamaji
Yoshihiko
Y
Ban
Masaaki
M
Ohta
Toshio
T
Ito
Shigeo
S
D000200:Action Potentials; D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D002245:Carbon Dioxide / Q000097:blood*; D005260:Female; D006863:Hydrogen-Ion Concentration; D006935:Hypercapnia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009433:Neural Inhibition; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000737:chemistry / Q000503:physiopathology*; D009435:Synaptic Transmission
D002245:Carbon Dioxide; D000241:Adenosine