Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our laboratory has reported previously the characteristics of specific AVP binding to rat hippocampal synaptic membranes (SPM) in the presence of Ni2+ [Costantini MG, Pearlmutter AF: J Biol Chem 259: 11739-11745, 1984]. We extended our investigation to determine the effects of Ni2+, (AVP), and AVP analogs on SPM protein phosphorylation. Ni2+ (5 mM) caused a dramatic reduction in phosphorylation of most SPM phosphoproteins. The most prominent protein which is phosphorylated in SPM has a molecular weight of 48 kilodaltons (KDa) and has been named B50 or F1; this protein shows altered phosphorylation in vitro in response to long-term potentiation in vivo as well as changes induced by exposure of SPM to ACTH (1-24), dopamine, and somatostatin. AVP and related peptides reduced phosphorylation of this pre-synaptic phosphoprotein in the following order of potency: AVP = oxytocin greater than DG-AVP greater than dDAVP greater than d(CH2)5Tyr(Me)AVP = [pGlu4,Cyt6]AVP-(4-9). Except for the pressor antagonist d(CH2)5Tyr(Me)AVP, this corresponds to their relative efficacy in displacing 3H-AVP from high-affinity specific binding sites on rat hippocampal synaptic membranes. Ni2+ did not alter the degree of inhibition caused by the peptides. When SPM were treated with AVP after the attainment of maximum 32P incorporation, AVP inhibited dephosphorylation over a 30-min period. Our results show that AVP can alter both phosphorylation and dephosphorylation of hippocampal SPM phosphoproteins in vitro; the direction of these effects depends upon experimental conditions. Since B50/F1 is known to be a substrate for protein kinase C, AVP may act by inhibition of protein kinase C activity, either directly or indirectly.
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PMID:Effects of arginine vasopressin on protein phosphorylation in rat hippocampal synaptic membranes. 303 58

The effect of arginine vasopressin (AVP) on protein phosphorylation in rat hippocampal synaptic plasma membranes (SPM) was examined. With a crude SPM preparation, AVP (10(-8)-10(-5) M) stimulated phosphorylation of a number of proteins which included a brain-specific protein of 48 kDa called B50 or protein F1, which is thought to be related to synaptic plasticity. Equimolar levels of oxytocin also stimulated B50/F1 phosphorylation. AVP and oxytocin at higher concentrations (10(-4)-10(-3) M) reduced SPM protein phosphorylation. When SPM was treated with both AVP and oxytocin, the effects were not additive; on the other hand, the effects of the phorbol ester (TPA) and AVP were additive. With SPM, partially purified by sucrose density centrifugation, only the inhibitory effect of AVP on B50/F1 phosphorylation was seen. These results suggest that AVP and oxytocin stimulation of B50/F1 phosphorylation requires cellular factors which are removed from SPM during membrane purification. In contrast, the inhibitory mechanism triggered by AVP and oxytocin appears to be associated with, or an integral part of, the synaptic membrane itself. Because the effects on membrane protein phosphorylation with maximal amounts of AVP and oxytocin were not additive, they must bind to the same sites on the membrane. This conclusion is supported by the additivity of the effects of AVP and phorbol ester, since the phorbol ester can act directly on the kinase and does not require a membrane recognition site.
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PMID:Protein phosphorylation in rat hippocampal synaptic plasma membranes in response to neurohypophyseal peptides. 379 Sep 90

Arginine vasopressin- (AVP) and oxytocin- (OXT) secreting magnocellular neurons undergo gross structural changes with chronic physiological stimulation. Here, we investigated subcellular aspects of plasticity in rat neurohypophysial terminals during dehydration. Ultrastructural analyses demonstrated that chronic dehydration by 2% NaCl drinking for 7 days significantly decreased the numbers of neurosecretory granules and microvesicles but not the numbers of mitochondria. Moreover, in dehydrated rats, terminals making neurovascular contacts enlarged, whereas terminals in apposition to astrocytes, i.e., neuroglial contacts, became smaller. Western blot analyses demonstrated significant decreases in the levels of F3 and Thy-1 together with those of AVP- and OXT-neurophysin, but the levels of synaptophysin, SNAP-25, and GAP-43 were unchanged. Both F3 and Thy-1 were recovered in the buffer-insoluble pellet, and phosphatidyl inositol-specific phospholipase C treatment released both molecules from the crude membrane fraction, indicating that they are attached to terminal membranes by glycosylphosphatidyl inositol anchors. Confocal microscopic observations demonstrated that F3 colocalized with Thy-1 in the same terminals of magnocellular neurons. In contrast, the level of calretinin, a Ca(2+) binding protein was significantly increased with chronic dehydration. Thus, the present results suggest that enhancement of neurovascular contacts results from rearrangement of terminal-astrocyte and terminal-vessel contacts rather than enlargement or sprouting of magnocellular terminals themselves. The down-regulation of F3 and Thy-1 may contribute to enhancement of neurovascular contacts that accompany increased peptide release during dehydration.
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PMID:Plasticity of neurohypophysial terminals with increased hormonal release during dehydration: ultrastructural and biochemical analyses. 1134 90

Central diabetes insipidus can occur after hypothalamic-hypophyseal tract injury. This injury is linked with a deficit in circulating vasopressin and oxytocin, which are produced in the supraoptic nuclei and the hypothalamic paraventricular nuclei. Previous studies indicate that an ectopic neural lobe forms after pituitary stalk lesion in rats, and while the relationship between an ectopic neural lobe and CDI outcomes is unclear, the underlying mechanisms are also unknown. Here, we report that two different CDI characteristics are shown in rats that underwent pituitary stalk electric lesion and are defined by two different groups classified as the recovery group and the no-recovery group. Rats showed an enlarged functional ectopic neural lobe at the lesion site with a low CDI index. Moreover, growth associated protein-43, p-PI3K and p-AKT were up-regulated in the unmyelinated fibers of the ectopic neural lobe. Our findings suggest that the enlarged structure formed a functional ectopic neural lobe after the pituitary stalk lesion, and its regeneration might influence the CDI outcome. This regeneration might be due to an increase in GAP-43 expression through the PI3K/AKT pathway.
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PMID:Functional ectopic neural lobe increases GAP-43 expression via PI3K/AKT pathways to alleviate central diabetes insipidus after pituitary stalk lesion in rats. 2948 90