Effects of metabolic fragments of [Arg⁸]-vasopressin on nerve growth in cultured hippocampal neurons

The effects of metabolic fragments of [Arg⁸]-vasopressin (AVP), [pGlu⁴, Cyt⁶]AVP (AVP_4-9), and desglycinamide-[pGlu⁴, Cyt⁶]AVP (AVP_4-8) on the growth of hippocampal neurons in culture were investigated in comparison with those of AVP. AVP_4-9 caused a significant increase in filopodial length following 96 h of exposure at concentrations higher than 300 nM. AVP_4-9 was more potent than AVP. AVP_4-8 also induced an increase in filopodial length, but this effect was less than that of AVP. The selective V₁ agonist [Phe², Ile³, Orn⁸]-vasopressin caused a significant increase in filopodial length, whereas the selective V₂ agonist [deamino-Cys¹, D-Arg⁸]-vasopressin showed no such effect. OPC-21268, a vasopressin V₁ antagonist, blocked AVP and AVP fragment-induced increases in filopodial length. However, the V₂ antagonist OPC-31260 showed no such effect. A23187, a representative Ca ionophore, also increased filopodial length, and the A23187-induced increase in filopodial length was potentiated by AVP and AVP fragments. These results indicated that AVP_4-9 and AVP_4-8 increased filopodial length in cultured hippocampal neurons by activating V₁ receptors. Both phenomena induced by AVP_4-9 and AVP_4-8 were associated with intracellular calcium mobilization. Copyright (C) 2000 Elsevier Science Inc.