Chronic infusion of agents that increase cyclic AMP concentration enhances the regeneration of mammalian peripheral nerves in vivo.
Our previous investigation indicates that forskolin, a robust activator of adenylate cyclase, promotes sensory nerve regeneration in amphibians. The present study was designed to determine if forskolin had a similar effect in mammals. We also wished to test the hypothesis that cyclic AMP modulates nerve regeneration by comparing the effects of chronically infused forskolin with the effects of infused dibutyryl cyclic AMP, 8-bromo cyclic AMP, and the phosphodiesterase inhibitor, theophylline. Our results indicated that all agents promoted some aspect of regeneration. The two which presumably generated the largest increase in cyclic AMP concentration, forskolin and 8-bromo cyclic AMP, had the most profound effect on axonal elongation. All agents decreased the time to sprout initiation, but theophylline produced the largest decrease and its effect was mimicked by caffeine, a methylxanthine with limited ability to inhibit phosphodiesterase. This suggests that sprout formation may be triggered by an increase in intraaxonal free Ca2+, possibly modulated by cyclic AMP. The role of cyclic AMP in axonal elongation remains to be determined, but may be associated with stimulation of protein synthesis in the nerve cell body.
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D006224:Cricetinae; D000242:Cyclic AMP / Q000502:physiology*; D004343:Drug Implants; D005260:Female; D008647:Mesocricetus; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000187:drug effects*; D059348:Peripheral Nerve Injuries; D010525:Peripheral Nerves / Q000187:drug effects; D012584:Sciatic Nerve / Q000293:injuries
D004343:Drug Implants; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D003994:Bucladesine; D000242:Cyclic AMP