PYRIMIDINOCEPTOR POTENTIATION BY ATP IN NG108-15 CELLS

Regulation of inositol phospholipid hydrolysis by UTP and UDP in neuro blastoma x glioma hybrid cell line NG108-15 was potentiated in the pre sence of ATP. The effect of ATP was dose dependent and shifted the EC5 0 value for these uracil nucleotides up to three powers of magnitude, having no influence on the maximal value of the response. Adenine nucl eotides (ADP, AMP, adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S), beta,gamma-methyleneadenosine 5'-triphosphate (beta gamma MeATP), 3'-O -(4-benzoyl)benzoyl ATP (BzATP) and 3'-deoxyadenosine 5'-O-(1-thio)tri phosphate (dATP alpha S)) as well as adenosine, had no influence on th e pyrimidinoceptor response. The potentiation effect was abolished by excess of EDTA. The results were in agreement with the hypothesis of p yrimidinoceptor affinity regulation via extracellular phosphorylation of the receptor protein, initiated by ATP. This mechanism may have phy siological implication for functioning of uracil nucleotides as endoge nous signaling molecules. (C) 1998 Federation of European Biochemical Societies.