Intercellular action of nitric oxide increases cGMP in cerebellar Purkinje cells.
cGMP is thought to play a role in cerebellar signalling yet its production within Purkinje cells has never been detected. In the present study, the hydrolysis of a fluorescent substrate analogue, 2'-O-anthranyloyl cyclic GMP, by type 5 phosphodiesterase was monitored within Purkinje cells in slices and in culture. Nitric oxide, either endogenously released from adjacent neurons or pharmacologically applied, accelerated the rate of hydrolysis in a manner that was dependent on soluble guanylyl cyclase, demonstrating that nitric oxide triggers cyclic GMP production in Purkinje cells, which in turn activates type 5 phosphodiesterase. We conclude that NO acts as an intercellular messenger in the cerebellar cortex and that parallel fibre terminals are a probable source of nitric oxide.
Hartell
N A
NA
Pharmaceutical Science Research Institute, Aston University, Birmingham, UK.
Furuya
S
S
Jacoby
S
S
Okada
D
D
D015106:3',5'-Cyclic-GMP Phosphodiesterases; D000818:Animals; D002478:Cells, Cultured; D002525:Cerebellar Cortex; D006152:Cyclic GMP / Q000378:metabolism*; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D004558:Electric Stimulation; D004622:Embryo, Mammalian; D005260:Female; D016166:Free Radical Scavengers / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology / Q000502:physiology*; D010727:Phosphoric Diester Hydrolases / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011689:Purkinje Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D016166:Free Radical Scavengers; D009569:Nitric Oxide; D010727:Phosphoric Diester Hydrolases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517384:Pde5a protein, rat; D006152:Cyclic GMP