neuromedin-n and Neuroblastoma

Neurotensin, some of its analogs, and neuromedin N were examined for comparison of their potencies at stimulating inositol phospholipid hydrolysis and cyclic GMP synthesis in intact murine neuroblastoma cells (clone N1E-115). Neurotensin(8-13) and acetylneurotensin(8-13) had the highest potencies for the stimulation of the hydrolysis of inositol phospholipid, which were about three times as potent as neurotensin (EC50 = 0.9 nM). On the other hand, fragments of the amino-terminal portion of neurotensin, such as neurotensin(1-6), neurotensin(1-8) and neurotensin(1-11), showed no ability to stimulate this hydrolysis. Neuromedin N, which is similar in structure to neurotensin(8-13) and which has been demonstrated to stimulate cyclic GMP formation [J.A. Gilbert and E. Richelson, Eur. J. Pharmac. 129, 379 (1986)], had EC50 values of 2.5 and 4.5 nM for release of [3H]inositol phosphates and stimulation of cyclic [3H]GMP respectively. A strong correlation was obtained between the EC50 values for neurotensin and several analogs in the stimulation of the release of inositol phosphates and the EC50 values for these peptides in the stimulation of cyclic GMP formation in neuroblastoma clone N1E-115 cells under similar experimental conditions. Thus, these two different biochemical effects of neurotensin and its analogs appear to be mediated by the same receptor site, which may also have been the site of action of neuromedin N in these cells.

Topics: Animals; Cell Line; Cyclic GMP; Inositol Phosphates; Mice; Neuroblastoma; Neurotensin; Peptide Fragments; Phosphatidylinositols

The naturally occurring analogs of neurotensin-(8-13), xenopsin, [Lys8,Asn9]neurotensin-(8-13) (LANT-6) and neuromedin N stimulated the production of intracellular cyclic GMP in murine neuroblastoma clone N1E-115, an adrenergic neuronal cell type. The order of potency was neurotensin-(8-13) greater than neurotensin greater than xenopsin greater than neuromedin N greater than LANT-6. Furthermore, xenopsin, LANT-6 and neuromedin N each inhibited the specific binding of [3H]neurotensin to intact N1E-115 cells in a dose-related fashion. The order of affinity of the peptides for the neurotensin receptor was neurotensin-(8-13) greater than xenopsin greater than neurotensin greater than neuromedin N greater than LANT-6.

Topics: Animals; Clone Cells; Cyclic GMP; Mice; Neuroblastoma; Neurotensin; Oligopeptides; Peptide Fragments; Peptides; Receptors, Neurotensin; Receptors, Neurotransmitter; Xenopus Proteins