argipressin-(4-8) and argipressin-(4-9)

Vasopressin (VP) undergoes a step-wise aminopeptidase conversion process in the brain, leading to accumulation of several metabolites. Some of these metabolites, in particular [pGlu4,Cyt6]VP 4-9 and 4-8, show behavioral effects comparable to VP, but are more potent and selective than VP. Most data favor the existence of a separate receptor for the VP metabolites distinct of the classical VP and oxytocin receptors, although its identity has remained obscure thus far. The characterization of this receptor is a major challenge to understand how the brain VP system generates and regulates divers central functions.

Topics: Animals; Arginine Vasopressin; Brain; Brain Chemistry; Hormone Antagonists; Peptide Fragments

The effects of vasopressin (VP), VP fragments and propressophysin glycopeptide on neuronal activities in the septum-hippocampus complex of rats were studied in vitro and in vivo. The frequency of the hippocampus theta rhythm in Brattleboro rats homozygous for diabetes insipidus was significantly slower than that of heterozygous litter mates and normal rats. Intracerebroventricular micro-injection of des-glycine-amide vasopressin corrected for several hours the frequency deficit of the theta rhythm in the homozygous Brattleboro rats and the centrally administered VP slowed down theta rhythm in normal rats. Microinotophoretically administered VP excited single neurons in the lateral septum of ventral hippocampus, and/or facilitated the responses of these neurons to glutamate and to stimulation of the glutamatergic afferent fibers in the fimbria bundle. The excitatory effects of VP vanished within seconds after termination of the peptide administration, however, the peptide-induced enhancement of glutamate and syntatically induced excitations were sustained for up to 60 min after the peptide administration. In vitro, pM concentrations of VP, VP 4-8 and C-terminus glycopeptide of propresophysin facilitated for 30-60 min the glutamate-mediated EPSPs in neurons of the lateral septum or the ventral hippocampus. The EPSPs increase in the lateral septum neurons was not prevented by pretreatment with antagonist of the V1a type of the vasopressin receptor. The resting membrane potential and input resistance were not affected by the peptides. A low-frequency electrical stimulation in the diagonal Band of Broca or in the Bed nucleus of the stria terminals, sources of the vasopressinergic innervation of the septum, facilitated the negative wave of the filed potentials responses evoked in the lateral septum by stimulating the fimbria bundle fibers in control Long-Evans and Brattleboro rats heterozygous for diabetes insipidus. The field potential increase was sustained for several hours after the stimulation, and it was not occluded by long-term potentiation elicited by high frequency stimulation of the fimbria bundle afferent fibers. Brattleboro rats homozygous for diabetes insipidus failed to show the filed potential increase after the diagonal band stimulation. It is suggested that the long-lasting facilitation of glutamate-mediated excitations might be a physiological action of the propressophysin-derived peptides in the septum-hippocampus complex which, in concert w

Topics: Animals; Arginine Vasopressin; Excitatory Postsynaptic Potentials; Hippocampus; Hormone Antagonists; In Vitro Techniques; Neurons; Peptide Fragments; Rats; Septal Nuclei

The effects of endogenous metabolites of the neuropeptide vasopressin (VP) in behavioural tests led to the hypothesis that VP metabolites have a more selective function than VP. In contrast to VP, no peripheral effects have been found thus far with VP metabolites and their function seems to be associated with memory-related behaviour. VP metabolites can improve both consolidation and retrieval of memory. Effects on autonomic and electrophysiological parameters and interactions with other neurotransmitter systems have provided some information about the processes that could underlie the effects of VP metabolites on memory-related behaviour. There is evidence that the effects of VP metabolites could be mediated by a VP metabolite receptor, which is different from the known VP receptors. The VP metabolite receptor could be a link between the neuropeptide VP and memory-related behaviour.

Topics: Animals; Arginine Vasopressin; Brain; Brain Chemistry; Maze Learning; Memory; Peptide Fragments

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 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 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) antagonist, blocked AVP and AVP fragment-induced increases in filopodial length. However, the V(2) 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 V(1) receptors. Both phenomena induced by AVP(4-9) and AVP(4-8) were associated with intracellular calcium mobilization.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Arginine Vasopressin; Calcimycin; Cell Division; Cells, Cultured; Embryo, Mammalian; Female; Hippocampus; Microscopy, Fluorescence; Neurons; Peptide Fragments; Rats; Rats, Wistar; Receptors, Vasopressin