A nucleotide receptor that mobilizes Ca2+ in the mouse submandibular salivary cell line ST885.

1. We have identified a Ca(2+)-mobilizing receptor that responds to extracellular ATP (0.1-1000 microM) 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 microM and for UTP of 4.6 microM. 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 microM) 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 microM), it failed to antagonize the effects of near maximal concentrations of ATP or UTP. We conclude that 2-methylthio ATP acts upon a distinct receptor.