Le. Trudeau, Neurotensin regulates intracellular calcium in ventral tegmental area astrocytes: Evidence for the involvement of multiple receptors, NEUROSCIENC, 97(2), 2000, pp. 293-302
Recent evidence suggests that some types of neurotensin receptors may be ex
pressed by astrocytes. In order to explore the function of neurotensin rece
ptors in astrocytes, the effect of a neurotensin receptor agonist, neuroten
sin(8-13), on intracellular Ca2+ dynamics in mixed neuronal/glial cultures
prepared from rat ventral tegmental area was examined. It was found that ne
urotensin(8-13) induces a long-lasting rise in intracellular Ca2+ concentra
tion in a subset of glial fibrilary acidic protein-positive glial cells. Th
is response displays extensive desensitization and appears to implicate bot
h intracellular and extracellular Ca2+ sources. In the absence of extracell
ular Ca2+, neurotensin(8-13) evokes only a short-lasting rise in intracellu
lar Ca2+. The neurotensin-evoked intracellular Ca2+ accumulation is blocked
by the phospholipase C inhibitor U73122 and by thapsigargin, suggesting th
at it is initiated by release of Ca2+ from an inositol triphosphate-depende
nt store. The Ca2+-mobilizing action of neurotensin(8-13) in astrocytes is
dependent on at least two receptors, because the response is blocked in par
t only by SR48692, a type 1 neurotensin receptor antagonist, and is blocked
completely by SR142948A, a novel neurotensin receptor antagonist. The find
ing that the type 2 neurotensin receptor agonist levocabastine fails to mim
ic or alter the effects of neurotensin(8-13) on intracellular Ca2+ makes it
unlikely that the type 2 neurotensin receptor is involved.
In summary, these results show that functional neurotensin receptors are pr
esent in cultured ventral tegmental area astrocytes and that their activati
on induces a highly desensitizing rise in intracellular Ca2+. The pharmacol
ogical profile of this response suggests that a type 1 neurotensin receptor
is involved but that another, possibly novel, non-type 2 neurotensin recep
tor is also implicated. If present in vivo, such signalling could be involv
ed in some of the physiological actions of neurotensin. (C) 2000 IBRO. Publ
ished by Elsevier Science Ltd.