Neurotensin stimulates polyphosphoinositide breakdown and prolactin release in anterior pituitary cells in culture.
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.
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
D007295:Inositol Phosphates; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D009496:Neurotensin; D011388:Prolactin