Effect of diadenosine polyphosphates in achondroplasic chondrocytes: inhibitory effect of Ap4A on FGF9 induced MAPK cascade.

Achondroplasia is characterised by a mutation in the gene that encodes for the FGF receptor type 3 (FGFR3), producing a hyperactivation of this receptor and a subsequent increase in MAPK activity. We have tested the ability of nucleotides to decrease the activation of MAPK in chondrocytes with achondroplasic FGFR3 receptor. Diadenosine tetraphosphate, Ap(4)A, reduced the phosphorylation of pERK1/2 triggered by FGF9 (38% reduction). Ap(4)A diminished the expression of achondroplasic FGFR3 receptor (65% reduction), stimulating FGFR3 receptor degradation. The action of Ap(4)A seems to be mediated by a dinucleotide receptor rather than by any other ATP receptor.