Neurotensin and its analogs—Correlation of specific binding with stimulation of cyclic GMP formation in neuroblastoma clone N1E-115

Characterization of the effect of SR48692 on inositol monophosphate, cyclic GMP and cyclic AMP responses linked to neurotensin receptor activation in neuronal and non‐neuronal cells

“…In our study, we show that neurotensin inhibited cyclic AMP levels stimulated by forskolin with an EC50 of 1.3 nM. This result is in agreement with previous work using prostaglandin El to stimulate cyclic AMP production (Bozou et al, 1986), but contrasts with the failure to report an effect of neurotensin on this nucleotide response (Goedert et al, 1984;Gilbert et al, 1986). The reasons for these discrepancies are still obscure.…”

“…In the human colonic carcinoma cell line, HT29, the binding of neurotensin to its receptor leads to an increase in phosphatidyl inositol turnover without affecting cyclic nucleotide levels ). In contrast, in the electrically excitable mouse neuroblastoma NlE115, neurotensin was found to increase inositol phosphates (Snider et al, 1986) and intracellular concentrations of guanosine 3':5'-cyclic monophosphate (cyclic GMP) (Gilbert et al, 1986) and to decrease adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels (Bozou et al, 1986). Furthermore, in Chinese hamster ovary cells transfected with the rat neurotensin receptor (rNTRCHO), neurotensin was reported to stimulate the production of inositol phosphates (Hermans et al, 1992;Watson et al, 1992) as well as the formation of cyclic AMP (Yamada et al, 1993).…”

Rational design of novel neurotensin mimetics: Discovery of a pharmacologically unprecedented agent exhibiting concentration-dependent dual effects as antagonist and full agonist

“…It is important to note that the replacement of Pro I° in NT(8-13) with D-proline leads to a structure that fails to exhibit either binding or functional activities in the micromolar range and that the synthesized Arg-Arg-Pro mimetics and the tetrapeptide fragment Pro-Tyr-Ile-Leu were found to be inactive [24,30]. These findings rule out the possibility that even major structural changes to the Arg-Arg-Pro portion may be inconsequential to receptor recognition, and exclude the speculation that equally potent compounds could have just as easily been found by randomly preparing structures with two charged functional groups.…”

“…In the application of the MTA to the design of NT(8-13) mimetics, Pro 1° was assigned as a spacer residue, since an NT analog possessing D-proline substitution for Pro ~° gave no response at 1 gM concentrations in binding and functional assays [30]. This role for Pro ~° is also reasonable because its five-membered ring fixes the dihedral angle between C ~ and the ring nitrogen to a small range of about +20 °.…”

Potentiatin by Neurotensin of Carbachol-Induced Tension Development in .BETA.-Escin-Skinned Smooth Muscle of Guinea-Pig Ileum.

“…60(11): 1227-1232, 1998 48692 inhibits the NT-induced contraction and relaxation with significantly-different potencies [23]. These observations suggest the possible existence of distinct NT receptor subtypes.In some cellular models including mouse neuroblastoma N1E115 cells, evidence has been provided that NT receptors couple to G proteins and that the receptor activation causes mobilization of intracellular Ca 2+ , stimulation of inositol phosphates and of cyclic GMP formation, and inhibition of cyclic AMP formation [1,4,9,11,27]. All the NT receptormediated events in cellular models are reported to be blocked by SR 48692 [11,27].…”