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

1 We have identified a Ca2+-mobilizing receptor that responds to extra cellular ATP (0.1 - 1000 muM) in a salivary epithelial cell line (ST88 5). The activated receptor also stimulates Ca2+ entry from the extrace llular fluid. 2 The receptor shows an agonist selectivity profile cons istent with the behaviour of the nucleotide receptor class. In particu lar, the pyrimidine nucleotide, UTP, was equipotent with ATP. 3 Analys is of concentration-response data for the ATP and UTP-activated recept or using the Hill equation yielded EC50 values (concentrations of agon ist inducing a half-maximal response) for ATP of 4.2 muM and for UTP o f 4.6 muM. 4 ATP and UTP induced cross-desensitization and were not ad ditive when administered simultaneously at maximal concentration. Thes e findings are consistent with the hypothesis that both nucleotides ac t upon a common receptor. 5 The ATP analogue, 2-methylthio ATP, mobili zed 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 a gonist 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