Platelet activating factor modulates signal transduction in Dictyostelium

Abstract

During development, Dictyostelium discoideum cells produce platelet activating factor (PAF). When cells are stimulated with external cAMP pulses, PAF is transiently synthesized. To determine whether PAF is involved in signal transduction, we have tested the effect of PAF on some cellular responses which are regulated by cAMP, such as spontaneous light-scattering oscillations of suspended cells, cAMP relay, transient increases of cGMP level, and extracellular calcium uptake. Our results show that PAF specifically interferes with spontaneous spike-shaped oscillations, without affecting sinusoidal ones. PAF increases the amplitude of a spike, but has no effects on its phase or frequency. When cells fail to oscillate spontaneously, PAF does not induce spikes; however, if administered together with cAMP, it amplifies the light-scattering response to cAMP. Amplification of light-scattering changes is accompanied by a threefold increase in the concentration levels of both cellular cAMP and cGMP. Extracellular Ca2+ uptake is also stimulated by PAF. This latter response is independent of endogenous or exogenously added cAMP. All these effects are specific for the naturally occurring R-enantiomer of PAF, the S-enantiomer and lyso-PAF being inactive. These results suggest that PAF modulates signal transduction in Dictyostelium, probably by interacting with an intracellular acceptor, which is involved in the pathways regulating membrane Ca2+ channels, adenylate and guanylate cyclase.