Abstract
Second messenger calcium responses to the neuropeptide neurotensin and its non-peptide antagonist SR 48692 were studied in relation to the proliferation of pancreatic cancer cells. Neurotensin caused a transient increase in intracellular calcium in two pancreatic lines, MIA PaCa-2 and PANC-1, with EC50 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 changes with an IC50 (at 25 nM neurotensin) of 4.9 and 4.1 nM in MIA PaCa-2 and PANC-1 cells, respectively. In MIA PaCa-2 cells, SR 48692 may act as an inverse agonist as it depressed basal calcium. SR 48692 inhibited growth of both MIA PaCa-2 and PANC-1 cells. Only in MIA PaCa-2 cells did neurotensin overcome 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.
Original language | English (US) |
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Pages (from-to) | 213-219 |
Number of pages | 7 |
Journal | Anticancer Research |
Volume | 19 |
Issue number | 1 A |
State | Published - Apr 20 1999 |
Keywords
- Calcium
- Inverse agonist
- MIA PaCa-2
- Neurotensin
- PANC-1
- SR 48692
ASJC Scopus subject areas
- Oncology
- Cancer Research