Inosine reverses the inhibitory effects of the L-type Ca2+ channel antagonist, DM-BODIPY-dihydropyridine, on neuritogenesis in an in vitro rat superior cervical ganglia axotomy model.
It has recently been demonstrated that L-type calcium channel antagonism with the fluorescent dihydropyridine DM-BODIPY-dihydropyridine (DMBD) inhibits neurite regeneration in rat superior cervical ganglia (SCG). The neuritogenic effects of inosine have been described in various models and the mechanism is thought to be N-kinase dependent. Because of the final common pathway between calcium dependent and N-kinase dependent neurite regeneration it was hypothesized that inosine would increase regeneration in normally regenerating SCG and reverse the inhibitory effects of DMBD on regenerating SCG. An in vitro model of rat SCG injury, where mature neurites are transected and observed at 2 and 24 h, was used to assess the effects of inosine on DMBD treated neurons. Results demonstrate a significant inhibition of growth in DMBD treated cultures, significantly increased growth in the inosine + DMBD treated SCG over DMBD treated cells and significantly increased growth in the inosine alone treated group over control cells. There is also evidence that inosine + DMBD treatment promotes linear growth of neurites. The implications of the findings are discussed.
Cook
Douglas J
DJ
Division of Cellular and Molecular Biology, Toronto Western Research Institute, 399 Bathurst Street, Toronto, Ontario M5T 2S8, Canada.
Kulbatski
Iris
I
Tator
Charles H
CH
D000818:Animals; D019771:Axotomy; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000378:metabolism* / Q000502:physiology; D002452:Cell Count / Q000379:methods; D002478:Cells, Cultured; D004095:Dihydropyridines / Q000494:pharmacology*; D007288:Inosine / Q000494:pharmacology*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D016501:Neurites / Q000187:drug effects* / Q000502:physiology; D010627:Phenethylamines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000187:drug effects* / Q000502:physiology
C089792:1,4-dihydro--2,6-dimethyl-4-(2-trifluoromethylphenyl)-3,5-pyridinedicarboxylic acid 2-(4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-3-(s-indacene)propionylamino)ethylethyl ester; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D004095:Dihydropyridines; D010627:Phenethylamines; D007288:Inosine