Vasopressin-induced calcium signaling in cultured hippocampal neurons.
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.(ABSTRACT TRUNCATED AT 250 WORDS)
Brinton
R D
RD
Department of Molecular Pharmacology and Toxicology, University of Southern California, Los Angeles 90033, USA.
Gonzalez
T M
TM
Cheung
W S
WS
D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D006624:Hippocampus / Q000378:metabolism* / Q000502:physiology; D007295:Inositol Phosphates / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017483:Receptors, Vasopressin / Q000819:agonists*; D015398:Signal Transduction / Q000502:physiology*
D007295:Inositol Phosphates; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; C002647:inositol 1-phosphate; D002118:Calcium