Previously, one type of human
neurotensin receptor has been molecularly cloned. Recently, it has been proposed that a subtype of
neurotensin receptor exists, which is not sensitive to newly synthesized
neurotensin receptor antagonist
SR 48692. In this study, we characterize the pharmacological properties of
neurotensin receptor expressed in human
pancreatic cancer cells, MIA PaCa-2. In binding studies with [3H]
neurotensin, the data fit a model for a single population of high-affinity binding sites that are competitively antagonized by
SR 48692. The rank order of the equilibrium dissociation rate constants for neurotensin(8-13),
neurotensin,
neuromedin N, [Ala11] neurotensin(8-13), and
SR 48692 were similar to those found with the molecularly cloned human
neurotensin receptors. Additionally, the intracellular
calcium mobilization and the growth of MIA PaCa-2 cells induced by
neurotensin receptor agonist were completely inhibited by
SR 48692. In conclusion, our results showed that MIA PaCa-2 cells express functional and SR 48692-sensitive-type
neurotensin receptors. It is suggested that the
neurotensin receptor antagonist
SR 48692 may be useful in the treatment of
pancreatic cancers that possess this type of
neurotensin receptor.