We have previously demonstrated that nitric oxide (NO)-generating compounds inhibit D. discoideum differentiation by preventing the initiation of cAMP pulses (Tao, Y., Howlett, A. and Klein, C. (1996) Cell. Signal. 8, 37–43). In the present study, we demonstrate that cells produce NO at a relatively constant rate during the initial phase of their developmental cycle. The addition of oxyhemoglobin, an NO scavenger, stimulates cell aggregation, suggesting that NO has a negative effect on the development of aggregation competence. Starvation of cells in the presence of glucose, which has been shown to prevent the initiation of cAMP pulses (Darmon, M. and Klein, C. (1978) Dev. Biol. 63, 377–389), results in an increased production of NO. The inhibition of cell aggregation by glucose treatment can be reversed by oxyhemoglobin. These findings indicate that NO is a signaling molecule for D. discoideum cells and that physiological or environmental conditions that enhance external NO levels will delay the initiation of cAMP pulses, which are essential for cell differentiation.
ATP Triggers Human Th9 Cell Differentiation via Nitric Oxide-Mediated mTOR-HIF1α Pathway