Eur J Neurosci. 1991;3(4):379-382. doi: 10.1111/j.1460-9568.1991.tb00825.x.
The European journal of neuroscience
Eric Southam, John Garthwaite
PMID: 12106196 DOI: 10.1111/j.1460-9568.1991.tb00825.x
Exposure of adult rat cerebellar slices to a moderately raised K+ concentration (15 mM) caused a large (30-fold) rise in the levels of cyclic GMP. Excitatory amino acid antagonists failed to inhibit this response, nor could it be mimicked by agonists active at a number of other transmitter receptors. It was, however, inhibited by the nitric oxide (NO) synthase antagonist, l-methylarginine (IC50=10 microM), and also by tetrodotoxin (1 microM) implying that underlying the cyclic GMP response was an action potential-dependent formation of NO. Prelesioning of climbing fibres resulted in a loss of approximately 50% of the response to K+ but failed to influence the effects of glutamate receptor agonists or the NO-donor, nitroprusside. These findings point to a new mechanism for the formation of NO in the central nervous system and suggest that, in the cerebellum, climbing fibres are a source of NO.
