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 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.
Herzig
M C
MC
Cancer Therapy and Research Center, Institute for Drug Development, San Antonio, TX 78245, USA.
Chapman
W G
WG
Sheridan
A
A
Rake
J B
JB
Woynarowski
J M
JM
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D004533:Egtazic Acid / Q000494:pharmacology; D006801:Humans; D009496:Neurotensin / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011720:Pyrazoles / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology*; D018028:Receptors, Neurotensin / Q000037:antagonists & inhibitors* / Q000502:physiology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D011720:Pyrazoles; D011804:Quinolines; D018028:Receptors, Neurotensin; C079087:SR 48692; D009496:Neurotensin; D004533:Egtazic Acid; D002118:Calcium