Cyclic nucleotide-induced migration of electropermeabilized neutrophils: The effect of phosphodiesterase-resistant analogues

Objective: To study the effect of cyclic nucleotides and PDE-resistant cyclic nucleotide analogues on neutrophil migration. Methods: Migration of electropermeabilized neutrophils in Boyden chambers in vitro. Results: Addition of cyclic AMP inhibited migration of electropermeabilized neutrophils in the presence of cGMP, relative to the level of migration in the presence of cGMP alone. However, when cGMP was replaced with 8-pCPT-cGMP or Sp-cGMPS, analogues of cGMP which are not degraded by phosphodiesterases, cAMP synergistically enhanced migration. In contrast, migration in the presence of the phosphodiesterase-resistant cAMP analogue, Sp-cAMPS, was not enhanced by addition of cGMP. Conclusions: Taking into account reports in the literature which show that cGMP-hydrolysing activity can be enhanced by the catalytic subunit of cAMP-dependent protein kinase, it is hypothesized that breakdown of cGMP in neutrophils may be modulated via cAMP.