TY - JOUR
T1 - Pharmacological characterization of SR 48692 sensitive neurotensin receptor in human pancreatic cancer cells, MIA Paca-2
AU - Yamada, M.
AU - Ohata, H.
AU - Momose, K.
AU - Yamada, M.
AU - Richelson, E.
PY - 1995
Y1 - 1995
N2 - 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.
AB - 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.
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M3 - Article
C2 - 8581347
AN - SCOPUS:0028971041
VL - 90
SP - 37
EP - 47
JO - Research Communications in Chemical Pathology and Pharmacology
JF - Research Communications in Chemical Pathology and Pharmacology
SN - 1078-0297
IS - 1
ER -