A NUCLEOTIDE RECEPTOR THAT MOBILIZES CA2+ IN THE MOUSE SUBMANDIBULAR SALIVARY CELL-LINE ST(885)

1 We have identified a Ca2+-mobilizing receptor that responds to extracellular ATP (0.1 - 1000 muM) in a salivary epithelial cell line (ST885). The activated receptor also stimulates Ca2+ entry from the extracellular fluid. 2 The receptor shows an agonist selectivity profile consistent with the behaviour of the nucleotide receptor class. In particular, the pyrimidine nucleotide, UTP, was equipotent with ATP. 3 Analysis of concentration-response data for the ATP and UTP-activated receptor using the Hill equation yielded EC50 values (concentrations of agonist inducing a half-maximal response) for ATP of 4.2 muM and for UTP of 4.6 muM. 4 ATP and UTP induced cross-desensitization and were not additive when administered simultaneously at maximal concentration. These findings are consistent with the hypothesis that both nucleotides act upon a common receptor. 5 The ATP analogue, 2-methylthio ATP, mobilized Ca2+ ions with higher potency (EC50 = 0.23 muM) but lower efficacy than either ATP or UTP. However, 2-methylthio ATP was not a partial agonist of the ATP/UTP receptor. At maximal concentration (30 muM), it failed to antagonize the effects of near maximal concentrations of ATP or UTP. We conclude that 2-methylthio ATP acts upon a distinct