Suppression of the induction of long-term depression by carbon monoxide in rat cerebellar slices.
Carbon monoxide (CO) suppresses brain functions at doses lower than that suppressing oxygen (O(2)) supply to the brain, and the cerebellum is one of the sites most susceptible to the neurotoxic effects of CO. We investigated the effects of CO on the induction of cerebellar long-term depression (LTD) in the synapses between parallel fibres (PFs) and Purkinje cells. CO, at concentrations between 8 nM and 5 microM, exhibited almost no effect on synaptic responses in Purkinje cells, O(2) consumption and NO release from PFs in rat cerebellar slices. However, the induction of LTD was significantly suppressed by CO at concentrations between 40 and 200 nM. The suppressive effect of 40 nM CO was antagonized by 10 microM NOR3, an NO donor. In contrast, CO exhibited no clear effect on the induction of LTD at concentrations between 1 and 5 microM. The induction of LTD, suppressed by 10 microM N(G)-nitro-L-arginine, an inhibitor of NO synthase, was not restored by 5 microM CO. CO is not only a neurotoxic substance but also a candidate for an intercellular messenger. delta-Aminolevulinate (30 microM), a substance facilitating endogenous CO production, suppressed the induction of LTD, and the effect of delta-aminolevulinate was antagonized by 10 microM NOR3. These findings suggest that CO may have a suppressive effect on the induction of cerebellar LTD at nanomolar concentrations, probably via its effects on NO/cGMP signalling.
Shibuki
K
K
Department of Neurophysiology, Brain Research Institute, Niigata University, Asahi-machi, Niigata 951-8585, Japan. shibuki@bri.niigata-u.ac.jp
Kimura
S
S
Wakatsuki
H
H
D000622:Aminolevulinic Acid / Q000494:pharmacology; D000818:Animals; D002248:Carbon Monoxide / Q000494:pharmacology*; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects; D006152:Cyclic GMP / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D009924:Organ Culture Techniques; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D017319:Photosensitizing Agents / Q000494:pharmacology; D011162:Porphobilinogen / Q000494:pharmacology; D011689:Purkinje Cells / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D017319:Photosensitizing Agents; D009569:Nitric Oxide; D011162:Porphobilinogen; D002248:Carbon Monoxide; D000622:Aminolevulinic Acid; D006152:Cyclic GMP