title: Neurotensin stimulates polyphosphoinositide breakdown and prolactin release in anterior pituitary cells in culture.
abstract: Biochemical events underlying neurotensin action at the pituitary were investigated in primary culture of anterior pituitary cells prelabeled with [3H]inositol. Incubation with the tridecapeptide produced a dose-dependent increase in the content of total [3H]inositol phosphates. The time-course showed that the effect was rapid and significant within 1 min. Fractionation of [3H]inositol phosphates revealed that inositol triphosphate (IP3) and inositol diphosphate (IP2) increased earlier than inositol monophosphate (IP1). Structure/activity correlation studies demonstrated the specificity of neurotensin effect, showing that acetylneurotensin(8-13) displayed an action similar to the natural peptide, while neurotensin(1-6) hexapeptide did not exhibit any effect. The neurotensin analog [D-Trp11]-neurotensin antagonized in a concentration-dependent manner the effect of neurotensin both on prolactin release and on [3H]inositol phosphate production. The loss of prelabeled phosphoinositides was also investigated. Phosphatidylinositol-4,5-bisphosphate (PtdIns-4,5-P2) and phosphatidylinositol-4-phosphate (PtdIns-4-P) decreased significantly within 15 s, while a slight decline in phosphatidylinositol (PtdIns) level appeared only 1 min after neurotensin addition. These results suggest that neurotensin action at the pituitary is mediated by the early hydrolysis of polyphosphoinositides, leading to the production of 1,2-diacylglycerol and inositol phosphates which may initiate intracellular processes responsible for hormonal release.
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002855:Chromatography, Thin Layer; D005260:Female; D007295:Inositol Phosphates / Q000378:metabolism; D009496:Neurotensin / Q000494:pharmacology*; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols / Q000378:metabolism*; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D007295:Inositol Phosphates; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D009496:Neurotensin; D011388:Prolactin