title: Neurotensin induces the release of prostacyclin from human umbilical vein endothelial cells in vitro and increases plasma prostacyclin levels in the rat.
abstract: Human umbilical vein endothelial cells express high affinity neurotensin receptors which are coupled to phosphoinositide turnover and 45Ca2+ efflux (Schaeffer et al., 1995. J. Biol. Chem. 270, 3409-3413). In order to assess the physiological significance of neurotensin receptor activation in endothelial cells, we have compared the in vitro effect of neurotensin on prostacyclin release and cytosolic free calcium increase ([Ca2+]i) as determined by fura-2 fluorescence experiments to the in vivo effect of neurotensin on blood pressure and haematocrit. Neurotensin increased [Ca2+]i levels at low concentrations (EC50 = 4.2 +/- 0.2 nM, n = 3). At similar concentrations, neurotensin was also able to induce prostacyclin release from human umbilical vein endothelial cells (EC50 = 14 +/- 1 nM, n = 3) as determined by a 6-keto-prostaglandin F1 alpha enzyme immunoassay. The neurotensin (100 nM)-induced [Ca2+]i increase and prostacyclin release were inhibited by the specific non-peptide neurotensin receptor antagonist SR 48692 at similar concentrations (IC50 = 41 +/- 16 nM and 86 +/- 17 nM, respectively, n = 3), confirming that these responses were mediated by high affinity neurotensin receptors. Intravenous injection of neurotensin (1-4 nmol/kg i.v.) in the rat resulted in a drop of blood pressure and increased haematocrit, and nearly doubled the plasma levels of 6-keto-prostaglandin F1 alpha, the stable metabolite of prostacyclin. Whereas indomethacin (10 mg/kg i.v.) pretreatment significantly reduced the effect of neurotensin on blood pressure, it did not alter its effect on haematocrit. These results suggest that prostacyclin release plays a role in the hypotensive effects of neurotensin, but is not involved in its effects on haematocrit.
authors.affiliation: Haemobiology Research Department, Sanofi Recherche, Toulouse, France.
authors.forename: P
authors.initials: P
authors.lastname: Schaeffer
authors.forename: M C
authors.initials: MC
authors.lastname: Laplace
authors.forename: V
authors.initials: V
authors.lastname: Prabonnaud
authors.forename: A
authors.initials: A
authors.lastname: Bernat
authors.forename: D
authors.initials: D
authors.lastname: Gully
authors.forename: L
authors.initials: L
authors.lastname: Lespy
authors.forename: J M
authors.initials: JM
authors.lastname: Herbert
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D011464:Epoprostenol / Q000097:blood / Q000378:metabolism*; D006400:Hematocrit; D006801:Humans; D008297:Male; D009496:Neurotensin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014471:Umbilical Veins / Q000378:metabolism*
chemical_list: D009496:Neurotensin; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D002118:Calcium