Nanomolar cyclic adenosine and guanosine monophosphates stimulate macrophage colony-stimulating factor responsiveness...

Both 3':5' cyclic adenosine monophosphate (cAMP) and 3':5' cyclic guanosine monophosphate (cGMP) stimulated colony-stimulating factor 1 (CSF-1)-dependent colony formation by murine two-signal-dependent progenitors without influencing colony formation by committed CSF-1-responsive progenitors. The stimulatory effect was optimal at 10(-9) M and did not diminish with increasing concentrations of the cyclic nucleotides. The membrane-permeating analogs dibutyryl cAMP and 8-Br-cGMP similarly augmented colony formation by the transitional progenitors at 10(-9) M; however, with increasing concentration, enhancement diminished with eventual inhibition of total colony formation at micromolar concentrations. Stimulation by the two cyclic nucleotides was mutually incompatible. The results indicate that physiological levels of extracellular cyclic nucleotides may significantly influence myelopoiesis. Furthermore, the results introduce the interesting possibility that stimulation, unlike inhibition, may be initiated through an extracytoplasmic mechanism that does not require direct activation of cytoplasmic cyclic nucleotide-dependent protein kinases.