The effect of folic acid on cAMP-elicited cAMP production in Dictyostelium discoideum

In Dictyostelium discoideum, folic acid serves as a chemoattractant, accelerates the appearance of several developmentally regulated enzymes, alters the phase of spontaneous light-scattering oscillations, and elicits increases in cGMP and cAMP. The effect of folic acid and pteridine analogs on rates of [³H]cAMP secretion, monitored by rapid perfusion, was studied. At low cell densities folic acid elicited only minimal [³H]cAMP secretion. At high cell densities, folic acid elicited greater increases in cellular cAMP and rates of [³H]cAMP secretion than did maximally effective doses of cAMP. Following pretreatment with 10^-8 M cAMP for 10 min or 10^-6 M cAMP for 2 min, no [³H]cAMP was secreted in response to folic acid. Conversely, pretreatment with folic acid did not impair subsequent responsiveness to 5 × 10^-9 M cAMP. Simultaneous addition of folic acid and cAMP increased the release of [³H]cAMP two- to threefold compared to control stimuli of the same concentration of cAMP. Pretreatment with a mixed stimulus attenuated the response to a subsequent increment in the cAMP concentration only if the higher cAMP stimulus did not include folic acid. The effects of folic acid are mimicked by the pteridine ring alone; analogs substituted at the 2- or 5-position are ineffective; non-reducible analogs are partially active. The observations presented here suggest significant differences in the mechanisms by which cAMP and folic acid stimulate cAMP production. Rather than there being separate receptors for each chemoattractant that interact in the same way with an intracellular pathway, it appears that folic acid and pteridine analogs potentiate the response to cAMP.