Effects of metabolic fragments of [Arg(8)]-vasopressin on nerve growth in cultured hippocampal neurons

The effects of metabolic fragments of [Arg(8)]-vasopressin (AVP), [pGlu(4), Cyt(6)]AVP (AVP(4-9)), and desglycinamide-[pGlu(4), Cyt(6)]AVP (AVP(4-8)) on the growth of hippocampal neurons in culture were investigated in compar ison with those of AVP. AVP(4-9) caused a significant increase in filopodia l length following 96 h of exposure at concentrations higher than 300 nM. A VP(4-9) was more potent than AVP. AVP(4-8) also induced an increase in filo podial length, but this effect was less than that of AVP. The selective V-1 agonist [Phe(2), Ile(3), Orn(8)]-vasopressin caused a significant increase in filopodial length, whereas the selective V-2 agonist [deamino-Cys(1), D -Arg(8)]-vasopressin showed no such effect. OPC-21268, a vasopressin V-1 an tagonist, blocked AVP and AVP fragment-induced increases in filopodial leng th. However, the V-2 antagonist OPC-31260 showed no such effect. A23187, a representative Ca ionophore, also increased filopodial length, and the A231 87-induced increase in filopodial length was potentiated by AVP and AVP fra gments. These results indicated that AVP(4-9) and AVP(4-8) increased filopo dial length in cultured hippocampal neurons by activating V-1 receptors. Bo th phenomena induced by AVP(4-9) and AVP(4-8) were associated with intracel lular calcium mobilization. (C) 2000 Elsevier Science Inc.