[Arg⁸]-vasopressin-induced increase in intracellular Ca²⁺ concentration in cultured rat hippocampal neurons

Changes in intracellular Ca²⁺ concentration ([Ca²⁺](i)) induced by [Arg⁸]-vasopressin (AVP) were studied in cultured rat hippocampal neurons by fura-2 fluorometry. AVP (10-1,000 nM) caused a dose-dependent increase in [Ca²⁺](i). The selective V₁ vasopressin receptor agonist [Phe², Ile³, Orn⁸]vasopressin also induced a significant increase in [Ca²⁺](i), whereas the selective V₂ vasopressin receptor agonist [deamino Cys¹, D-Arg⁸]- vasopressin showed no effect. The AVP-induced increase in [Ca²⁺](i) was inhibited by the selective V₁ vasopressin receptor antagonist d(CH₂)₅[Tyr²(Me), Arg⁸]-vasopressin and nonpeptide V₁ antagonist OPC- 21268. On the other hand, no antagonistic effects were observed with the V₂ vasopressin antagonist desglycinamide-[d(CH₂)₅, D-Ile², Ile⁴, Arg⁸]- vasopressin and nonpeptide V₂ antagonist OPC-31260. The increase in [Ca²⁺](i) induced by AVP was abolished after removal of extracellular Ca²⁺. In addition, AVP-induced [Ca²⁺](i) elevation was not affected by treatment with verapamil, which blocked the [Ca²⁺](i) increase induced by an isotonic high K⁺- medium (50 mM). However, ω-conotoxin GVIA completely inhibited the effect of AVP. These results suggested that the AVP-induced [Ca²⁺](i) increase in cultured rat hippocampal neurons is due to influx of Ca²⁺ through V₁ VP receptors coupled with N-type calcium channels.