Cyclic nucleotide fluctuations during newt limb regeneration depend on injury and nerve action

Impressive cyclic GMP accumulations have been previously observed in stump tissues of amputated newt forelimbs. The aim of the present study was to measure cGMP and cAMP levels in innervated and in denervated stumps, in order to detect a possible nervous influence on the cyclic nucleotide accumulation of stump tissues. Denervation experiments were carried out in amputated newt forelimbs. Tissue sampling was made at several intervals (3, 9, 14 and 20 days) and cyclic nucleotide levels were measured by RIA. Cyclic nucleotide levels of innervated unamputated animals served as controls. Cyclic GMP and cyclic AMP contents of innervated regenerating stumps were compared with cGMP and cAMP contents of contralateral denervated stumps. Results showed clearly that cGMP accumulation was sharply reduced by denervation while cAMP levels were less modified. We suggest that dedifferentiating cells are the main source for the stump accumulated cGMP which increases under nervous control.