Effect of Tetanus Toxin on Oxytocin and Vasopressin Release from Nerve Endings of the Neurohypophysis

Halpern, Jane; Habig, William H.; Trenchard, Holly; Russell, James T.

doi:10.1111/j.1471-4159.1990.tb05797.x

Cited by 21 publications

(7 citation statements)

References 36 publications

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“…Cellubrevin was found to be absent from SGs and thus its functional link to SG exocytosis is not well supported here. Our results are thus entirely consis tent with prior reports which showed vasopressin release from intact and permeabilized nerve endings to be de creased or blocked by treatment with tetanus neurotoxin [58][59][60]. The current findings support the functional link of SNARE proteins in the neuroendocrine stimulus-secre tion coupling mechanism by demonstrating the presence of these proteins in the peptidergic nerve endings and by their susceptibility to cleavage by the respective toxins.…”

Section: Discussionsupporting

confidence: 81%

Characterization and Distribution of SNARE Proteins at Neuroendocrine Nerve Endings

et al. 1996

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Substantial evidence now exists to support a defined complex of interacting proteins, comprised of soluble, vesicle and plasma membrane components, as the core of a general membrane fusion mechanism. Specializations to the general secretory model occur based on cell-specific differences in Ca²⁺ regulation, secretory organelle types and secretory dynamics. The variation in secretory properties may also result, in part, from isoform diversity and selective-pairing of the molecular components of the core complex. The present report attempts to identify the SNARE proteins found in isolated peptidergic nerve endings of the rat neurohypophysis. The results demonstrate the presence of synaptosomal-associated protein of 25 kD, syntaxin and synaptobrevin as membrane-associated proteins in these nerve endings. Furthermore, we have utilized sucrose density gradient subcellular fractionation and immunoprecipitation protocols to investigate the synaptobrevin isotypes present on secretory granules and to probe using electrophysiological methods their functional relationship to secretion. Secretory granules were found to contain only the synaptobrevin 2 isoform, although the nerve endings themselves were found to possess in addition, synaptobrevin 1 and the closely related protein cellubrevin. Analysis of the secretory characteristics of single nerve endings using membrane capacitance measurements together with Botulinum B toxin dialysis demonstrated the critical importance of synaptobrevin 2 to both the rapid exocytotic release and a slower secretory process, that perhaps includes secretory granule recruitment and priming, in these peptidergic nerve endings.

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Section: Discussionsupporting

confidence: 81%

Characterization and Distribution of SNARE Proteins at Neuroendocrine Nerve Endings

et al. 1996

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“…26 ,J6 In addition, data published on the inhibition of exocytosis from within nerve terminals or endocrine cells by the light chains of the neurotoxins imply that both synaptic vesicle and secretory granule membranes contain membrane pro teins attacked by the neurotoxins' light chains. I .2,16,18.48-51 However, the membrane composition of synaptic vesicles and secretory granules is different2 9 ,52 and only a few membrane proteins such as synaptotagmins have been reported to be present in both types of secretory vesicles.…”

Section: Link Between Tetanus Toxin Light Chain Synaptobrevin and Exmentioning

confidence: 99%

Exploring the functional domain and the target of the tetanus toxin light chain in neurohypophysial terminals

et al. 1994

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Abstract-The tetanus toxin light ehain blocks ealcium induced vasopressin release from neurohypophysial nerve terminals. Here we show that histidine residue 233 within the putative zine binding motif of the tetanus toxin light chain is essential for the inhibition of ellocytosis, in the rat. The zine chelating agent dipicolinic acid as weil as captopril, an inhibitor of zinc-dependent peptidases, counteract the effect of the neurotoxin. Synthetic peptides, the sequences of which correspond to motifs present in the cytoplasmic domain of the synaptic vesic1e membrane protein synaptobrevin land 2, prevent the effect of the tetanus toxin light ehain.Our results indicate that zine bound to the zine binding motif constitutes the active site of the tetanus toxin light chain. Moreover they suggest that c1eavage of synaptobrevin by the neurotoxin causes the inhibition of exocytotic release of vasopressin from secretory granules.

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“…Although OT receptors exist on both neurons and astrocytes in the SON (Wang and Hatton, 2006), OT could influence GFAP expression indirectly. Therefore, we further tested effects of OT on GFAP expression after treatment of slices with tetanus toxin (TeTx), an agent that blocks synaptic vesicle release from the OT-secreting system (Halpern et al, 1990;de Kock et al, 2003). As shown in Figure 5A, treatment of slices with TeTx (10 nM, 2-4 h) almost completely suppressed EPSCs (4.6 Ϯ 1.0 vs 0.4 Ϯ 0.2 events/s before and after TeTx; n ϭ 8) and blocked OT-evoked EPSC reduction (Wang and Hatton, 2007a), indicating effective suppression of synaptic vesicle release.…”

Section: Suckling-reduced Gfap By Direct Action Of Ot On Astrocytesmentioning

confidence: 99%

Astrocytic Plasticity and Patterned Oxytocin Neuronal Activity: Dynamic Interactions

Wang¹,

Hatton²

2009

J. Neurosci.

123

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Astroglial-neuronal interactions are important in brain functions. However, roles of glial fibrillary acidic protein (GFAP) in this interaction remain unclear in acute physiological processes. We explored this issue using the supraoptic nucleus (SON) in lactating rats. At first, we identified the essential role of astrocytes in the milk-ejection reflex (MER) by disabling astrocytic functions via intracerebroventricular application of L-aminoadipic acid (L-AAA). L-AAA blocked the MER and reduced GFAP levels in the SON. In brain slices, L-AAA suppressed oxytocin (OT) neuronal activity and EPSCs. Suckling reduced GFAP in immunocytochemical images and in Western blots, reductions that were partially reversed after the MER. OT, the dominant hormone mediating the MER, reduced GFAP expression in brain slices. Tetanus toxin suppressed EPSCs but did not influence OT-reduced GFAP. Protease inhibitors did not influence OT-reduced GFAP images but blocked the degradation of GFAP molecules. In the presence of OT, transient 12 mM K ϩ exposure, simulating effects of synchronized bursts before the MER, reversed OT-reduced GFAP expression. Consistently, suckling first reduced and then increased the expression of aquaporin 4, astrocytic water channels coupled to K ϩ channels. Moreover, GFAP molecules were associated with astrocytic proteins, including aquaporin 4, actin, and glutamine synthetase and serine racemase. GFAP-aquaporin 4 association decreased during initial suckling and increased after the MER, whereas opposite changes occurred between GFAP and actin. MER also decreased the association between GFAP and glutamine synthetase. These results indicate that suckling elicits dynamic glial neuronal interactions in the SON; GFAP plasticity dynamically reflects OT neuronal activity.

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Effect of Tetanus Toxin on Oxytocin and Vasopressin Release from Nerve Endings of the Neurohypophysis

Cited by 21 publications

References 36 publications

Characterization and Distribution of SNARE Proteins at Neuroendocrine Nerve Endings

Characterization and Distribution of SNARE Proteins at Neuroendocrine Nerve Endings

Exploring the functional domain and the target of the tetanus toxin light chain in neurohypophysial terminals

Astrocytic Plasticity and Patterned Oxytocin Neuronal Activity: Dynamic Interactions

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