Neurotensin is an antagonist of the human neurotensin NT2 receptor expressed in Chinese hamster ovary cells

Interactions between neurotensin receptors and G proteins

“…When this receptor was expressed in CHO cells, stimulation by SR48692 or another NTS1 antagonist, SR 142948A, increased InsP formation, calcium mobilization, arachidonic acid production and MAPK activity, but did not increase cAMP production [76]. In this study, neither the endogenous peptides, NT and neuromedin N, nor levocabastine exerted agonist activity, but instead antagonized the effects of the SR compounds.…”

“…Studies on the cloned human NTS2 [76] extended these first observations, further disclosing striking differences between NTS2 and NTS1. When this receptor was expressed in CHO cells, stimulation by SR48692 or another NTS1 antagonist, SR 142948A, increased InsP formation, calcium mobilization, arachidonic acid production and MAPK activity, but did not increase cAMP production [76].…”

“…NTS2 was cloned from three species: mouse [49], rat [15] and human [76]. However, probably based on this history, but also reinforced by its very unexpected properties, recognition of NTS2 as a true NT receptor has not been so easy to achieve.…”

“…Rodent [15,49] and human [76] NTS2s (416 and 410 amino acids, respectively) share only around 40% amino acid identities with the corresponding NTS1s, have shorter Nterminal extracellular tails and longer third intracellular loops. NTS2 corresponds to the previously described "low affinity NT binding site".…”

“…NTS2 corresponds to the previously described "low affinity NT binding site". Rodent NTS2s bind the histamine H1 antagonist levocabastine with high affinity, whereas human NTS2 presents lower affinity for this compound [15,49,76]. Affinity of NT for NTS2 is poorly sensitive to Na + and insensitive to GTP.…”