Neurotensin receptor-mediated inhibition of pancreatic cancer cell growth by the neurotensin antagonist SR 48692

Second messenger calcium responses to the neuropeptide neurotensin and its non-peptide antagonist SR 48692 were studied in relation to the proliferati on of pancreatic cancel cells. Neurotensin caused a transient increase in i ntracellular calcium in two pancreatic lines, MIA PaCa-2 and PANG-1, with E C50 values of 4.6 and 11.4 nM and peak calcium concentrations of 190 % and 470 % of basal levels, respectively. SR 48692 inhibited these calcium chang es with an IC50 (at 25 nM neurotensin) of 4.9 and 4.1 nM in MIA PaCa-2 and PANG-1 cells, respectively. In MIA PaCa-2 cells, SR 48692 may act as an inv erse agonist as it depressed basal calcium. SR 48692 inhibited growth of bo th MIA PaCa-2 and PANG-1 cells. Only in MIA PaCa-2 cells did neurotensin ov ercome this inhibition or stimulate proliferation. The results imply that, in MIA PaCa-2 cells, the neurotensin antagonist SR 48692 inhibits growth in a neurotensin receptor-mediated fashion.