Neurotensin(8-13), the carboxyl-terminal portion of
neurotensin, is 4-50 times more potent than native
neurotensin in binding to intact
neuroblastoma N1E-115 cells and human brain tissue and in stimulation of intracellular
cyclic GMP production and
inositol phospholipid hydrolysis in clone N1E-115 (Gilbert JA and Richelson E, Eur J Pharmacol 99: 245-246, 1984; Gilbert JA et al., Biochem Pharmacol 35: 391-397, 1986; Kanba KS et al., J Neurochem 46: 946-952, 1986; and Kanba KS and Richelson E, Biochem Pharmacol 36: 869-874, 1987). A series of novel analogs of
neurotensin (8-13) was synthesized, and a structure-activity study was done comparing the abilities of these
peptides to stimulate intracellular
cyclic GMP production in intact
neuroblastoma clone N1E-115 and to inhibit the binding of [3H]
neurotensin to these cells and to membranal preparations from human brain. A direct correlation was found for each analog between its EC50 for biochemical activity and its KD for binding ability in studies with clone N1E-115. Furthermore, a strong correlation existed for each
peptide between its KD for binding to
neurotensin receptors on these cells and its KD for binding to
neurotensin receptors in human brain tissue. In this study, the residues that were important to the biochemical and binding activities of
neurotensin (8-13) proved to be identical to the
amino acids that are necessary for the functional integrity of native
neurotensin (Gilbert JA et al., Biochem Pharmacol 35: 391-397, 1986.