Vasopressin-induced calcium signaling in cultured hippocampal neurons

Roberta Diaz Brinton, Tania M. Gonzalez, Wing S. Cheung

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

We recently demonstrated that the neural peptide vasopressin (AVP) can act as a neurotrophic factor for hippocampal nerve cells in culture. Because the neurotrophic effect of vasopressin is mediated by the V1 receptor [11], we investigated AVP activation of calcium signaling pathways in cultured hippocampal neurons. Results of this investigation demonstrate that exposure of cultured hippocampal neurons prelabeled with [3H]myo-inositol to vasopressin induced a significant accumulation of [3H]inositol-1-phosphate ([3H]IP1). The selective V1 vasopressin receptor agonist, [Phe2, Orn2]vasotocin, induced a significant accumulation of [3H]IP1 whereas a selective V2 vasopressin receptor agonist, [deamino1, d-Arg8]-vasopressin, did not. Moreover, V1 agonist-induced accumulation of [3H]IP1 was blocked by the selective V1 vasopressin receptor antagonist d(CH2)5 [Tyr(Me)2]-vasopressin. V1 agonist-induced accumulation of [3H]IP1 was concentration dependent and exhibited a steep inverted U-shaped curve that included both stimulation and inhibition of [3H]IP1 accumulation. Time course analysis of V1 agonist-induced accumulation of [3H]IP1 revealed significant increase by 20 min which continued to be significantly elevated for 60 min. Investigation of the effect of closely related peptides on [3H]IP1 accumulation indicated that the vasopressin metabolite peptide AVP4-9 and oxytocin significantly increased [3H]IP1 accumulation whereas the vasopressin metabolite peptide AVP4-8 did not. AVP4-9 and oxytocin induced [3H]IP1 accumulation were blocked by the V1 vasopressin receptor antagonist d(CH2)5 [Tyr(Me)2]-vasopressin. V1 receptor activation was associated with a pronounced rise in intracellular calcium. Results of calcium fluorometry studies indicated that V1 agonist exposure induced a marked and sustained rise in intracellular calcium that exhibited oscillations. Interestingly, absence of calcium in the extracellular medium abolished both the rise in intracellular calcium and the appearance of oscillations. The loss of the intracellular calcium signal is not due to a failure to induce PIP2 hydrolysis since activation of the phosphatidylinositol pathway occurred in the absence of extracellular calcium. V1 agonist (250 nM) induced a highly significant increase in 45Ca2+ uptake from the extracellular medium within 5 sec of exposure. 45Ca2+ uptake remained significantly greater than basal for 300 sec. The increase in 45Ca2+ uptake was followed by a significant inhibition of uptake by 20 min of exposure. These results indicate that in cultured hippocampal neurons, V1 vasopressin receptor activation leads to activation of the phosphatidylinositol signaling pathway, uptake of calcium from the extracellular medium and induction of complex intracellular calcium signals. These data provide the first step in delineating the biochemical mechanism that underlies vasopressin-induced neurotrophism.

Original languageEnglish (US)
Pages (from-to)174-180
Number of pages7
JournalBrain Research
Volume661
Issue number1-2
DOIs
StatePublished - Oct 24 1994
Externally publishedYes

Keywords

  • Calcium
  • Hippocampus
  • Inositol triphosphate
  • Learning and memory
  • Nerve cell growth
  • Neural peptide
  • V receptor
  • Vasopressin

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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