Metabolite Of Arginine-vasopressin Research Articles

Cloning of cytidine triphosphate: phosphocholine cytidylyltransferase mRNA upregulated by a neuropeptide arginine-vasopressin((4-8)) in rat hippocampus.

Neuropeptide arginine-vasopressin((4-8)) (AVP(4-8)) is a metabolite of arginine-vasopressin which has been shown to have potent memory-enhancing activity, facilitate neurite elongation and prolongate cell aging. Identification of differentially expressed genes in hippocampus induced by AVP(4-8) is important for understanding the molecular basis of AVP(4-8) function. Differential display PCR and 5'rapid amplification of cDNA Ends were used. One new full length cDNA encoding rat cytidine triphosphate: phosphocholine cytidylyltransferase (CCT) beta was thus obtained. Northern blot analysis demonstrated that it was upregulated by AVP(4-8) in mature rat hippocampus. The study of tissue distribution with reverse transcription PCR showed that the gene was abundant in brain. Since CCT catalyzes the formation of cytidine diphosphate choline, which was reported to have a beneficial therapeutic effect on Alzheimer's disease, so we speculated that AVP(4-8) may be a potential candidate for treating Alzheimer's disease by upregulating CCT mRNA level.

Intracellular Pathways of V1 and V2Receptors Activated by Arginine Vasopressin in Rat Hippocampal Neurons

To explore the intracellular pathways activated by vasopressin receptors, the effects of arginine vasopressin (AVP) and its analogues mediating glycine (Gly)-induced Cl(-) currents (I(Gly)) were examined in acutely dissociated rat hippocampal CA1 neurons using the whole-cell patch recording technique. AVP and its analogues inhibited I(Gly) in a concentration-dependent manner. The inhibitory actions of AVP(4-9) (AVP metabolite) and NC-1900 (AVP(4-9) analogue) were reversed by a V(1) receptor antagonist, or pretreatment with 1,2-bis(2-amino-5-fluorophenoxy)ethane-N,N,N', N'-tetraacetic acid. In contrast, these blocking procedures had no effect on the 1-desamino-8-D-AVP (DDAVP; V(2) agonist) action. A V(2) receptor antagonist did not block the inhibitory action of AVP(4-9) or NC-1900, but blocked that of DDAVP. The inhibitory action of AVP was completely blocked by the co-application of the V(1) and V(2) antagonists. The inhibitory action of NC-1900 was not affected by perfusion with a Ca(2+)-free external solution, but was strongly blocked by thapsigargin. The intracellular application of heparin or anti-inositol 1,4,5-triphosphate (IP(3)) also blocked the NC-1900 action. Furthermore, Ca(2+)/calmodulin (CaM) inhibitors blocked the NC-1900 action, while a CaM-dependent kinase II inhibitor and PKC modulators had no effect. 2',5'-Dideoxyadenosine (an adenylate cyclase inhibitor), H-89, and Rp-cAMPS blocked the inhibitory actions of NC-1900 and DDAVP. These results suggest that the activation of the V(1) receptor in the hippocampal neurons induces the production of IP(3), which releases Ca(2+) from the IP(3)-sensitive Ca(2+) storage sites. The Ca(2+) binds to CaM, resulting in the activation of Ca(2+/)CaM-sensitive adenylate cyclases. The activation of protein kinase A through the adenylate cyclase inhibits I(Gly).

Characterization of binding sites of a memory-enhancing peptide AVP(4–8) in rat cortical synaptosomal membranes

The pentapeptide pGlu-Asn-Cyt-Pro-Arg [AVP(4–8), termed ZNC(C)PR in this article] has been found as a metabolite of arginine-vasopressin (AVP) in rat brain and has been shown to have potent memory-enhancing activity and to yield a series of biochemical events in brain tissues. [ 35S]ZNC(C)PR was chemically synthesized with high specific activity (232 Ci/mmol), and specific binding sites for ZNC(C)PR were located in synaptosomal membrane preparations of rat brain. We identified a specific binding site for ZNC(C)PR with a K d of 3.12 n M and B max of 31 fmol/mg protein in anterior cortical synaptosomal membranes in the presence of 5m M Ni 2+. A comparison of synthetic analogues of ZNC(C)PR competing with [ 35S]ZNC(C)PR for binding to anterior cortical receptor are presented. ZDC(C)PR, a 2-aspartyl substitute of the 2-asparaginyl residue in ZNC(C)PR, had the most potent competition, but AVP did not show significant ability to compete for the receptor with ZNC(C)PR.

Functional evidence for an apical V1 receptor in rabbit cortical collecting duct.

In the rabbit cortical collecting duct (CCD) perfused in vitro, we recently found that luminal arginine vasopressin (AVP) hyperpolarizes the transepithelial voltage (Vt) and inhibits the hydrosmotic effect of basolateral AVP. The present study was undertaken to characterize the apical receptor of the CCD for AVP. In contrast to AVP, luminal application of 1-desamino-8-D-arginine vasopressin (DDAVP), a V2 agonist, did not significantly induce hyperpolarization. Luminal oxytocin (OXT) hyperpolarized Vt, interfering with the effect of superimposed luminal AVP, whereas [Thr4,Gly7]OXT, an OXT agonist, did not reproduce the effect of OXT. The effects of luminal AVP and OXT were abolished by [d(CH2)5,Tyr(Me)]-AVP, a V1 antagonist. Finally, luminal applications of AVP metabolite neuropeptides, pGlu-Asn-Cys(Cys)-Pro-Arg and pGlu-Asn-Cys(Cys)-Pro-Arg-Gly-NH2, were without effect on Vt. These data suggest that luminal AVP induces hyperpolarization through an apical V1 receptor but not through a V2 receptor or an OXT receptor.

Comparative effects of arginine vasopressin, [pGlu 4,Cyt 6]arginine vasopressin-(4–9) and nerve growth factor on maintenance of functional tolerance to ethanol in mice

Previous work has demonstrated that arginine vasopressin (AVP), acting in the CNS, can maintain functional tolerance to ethanol. We now show that the AVP metabolite peptide, [pGlu 4,Cyt 6]arginine vasopressin-(4–9), also maintains ethanol tolerance, with a potency similar to that of arginine vasopressin, while nerve growth factor has only a marginal effect. The effects of these peptides on ethanol tolerance correlate with their previously described ability to induce expression of the proto-oncogene, c-fos, in the septum, a putative mechanism underlying peptide effects on neuroadaptive processes.

Vasopressin is metabolized by a trypsinlike enzyme in guinea pig amniotic fluid.

We have demonstrated that arginine vasopressin (AVP) is degraded to desglycinamide AVP by a trypsinlike enzyme found in guinea pig amniotic fluid. Incubation of [3H]AVP with guinea pig amniotic fluid in vivo or in vitro produced a metabolite that comigrated on high-pressure liquid chromatography with desglycinamide AVP in three different buffer systems. Also, AVP antisera that cross-reacted with standard desglycinamide AVP could detect this amniotic fluid metabolite. Because the enzyme responsible for the cleavage of glycinamide from AVP was likely to be trypsin, experiments with aprotinin, a trypsin inhibitor, were conducted. Results demonstrated that the production of the amniotic fluid AVP metabolite could be completely blocked in the presence of the trypsin inhibitor. In addition, examination of amniotic fluid collected from fetuses in the second half of gestation (term = 68 days) showed that AVP could not be metabolized to desglycinamide AVP until after 52 days of gestation. In conclusion, AVP appears to be metabolized by a trypsinlike enzyme in amniotic fluid, and because trypsin is a general proteolytic enzyme, the amniotic compartment may also serve as a clearance site for other proteins.