title: Neurotensin regulates intracellular calcium in ventral tegmental area astrocytes: evidence for the involvement of multiple receptors.
abstract: Recent evidence suggests that some types of neurotensin receptors may be expressed by astrocytes. In order to explore the function of neurotensin receptors in astrocytes, the effect of a neurotensin receptor agonist, neurotensin(8-13), on intracellular Ca(2+) dynamics in mixed neuronal/glial cultures prepared from rat ventral tegmental area was examined. It was found that neurotensin(8-13) induces a long-lasting rise in intracellular Ca(2+) concentration in a subset of glial fibrilary acidic protein-positive glial cells. This response displays extensive desensitization and appears to implicate both intracellular and extracellular Ca(2+) sources. In the absence of extracellular Ca(2+), neurotensin(8-13) evokes only a short-lasting rise in intracellular Ca(2+). The neurotensin-evoked intracellular Ca(2+) accumulation is blocked by the phospholipase C inhibitor U73122 and by thapsigargin, suggesting that it is initiated by release of Ca(2+) from an inositol triphosphate-dependent store. The Ca(2+)-mobilizing action of neurotensin(8-13) in astrocytes is dependent on at least two receptors, because the response is blocked in part only by SR48692, a type 1 neurotensin receptor antagonist, and is blocked completely by SR142948A, a novel neurotensin receptor antagonist. The finding that the type 2 neurotensin receptor agonist levocabastine fails to mimic or alter the effects of neurotensin(8-13) on intracellular Ca(2+) makes it unlikely that the type 2 neurotensin receptor is involved. In summary, these results show that functional neurotensin receptors are present in cultured ventral tegmental area astrocytes and that their activation induces a highly desensitizing rise in intracellular Ca(2+). The pharmacological profile of this response suggests that a type 1 neurotensin receptor is involved but that another, possibly novel, non-type 2 neurotensin receptor is also implicated. If present in vivo, such signalling could be involved in some of the physiological actions of neurotensin.
authors.affiliation: Départements de Pharmacologie et de Psychiatrie, Centre de Recherche en Sciences Neurologiques, Centre de Recherche Fernand Seguin, Université de Montréal, 2900 Boulevard Edouard-Montpetit, Montréal, Canada. louis-eric.trudeau@umontreal.ca
authors.forename: L E
authors.initials: LE
authors.lastname: Trudeau
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004963:Estrenes / Q000494:pharmacology; D005682:Gadolinium / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D009496:Neurotensin / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D018028:Receptors, Neurotensin / Q000037:antagonists & inhibitors / Q000502:physiology*; D019284:Thapsigargin / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors; D017557:Ventral Tegmental Area / Q000166:cytology / Q000502:physiology*
chemical_list: D004963:Estrenes; D007093:Imidazoles; D010446:Peptide Fragments; D010880:Piperidines; D011760:Pyrrolidinones; D018028:Receptors, Neurotensin; C104418:SR 142948A; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D009496:Neurotensin; C054381:neurotensin (8-13); D019284:Thapsigargin; D005682:Gadolinium; D010738:Type C Phospholipases; C047340:levocabastine; D000218:Adamantane; D002118:Calcium