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Molecular and pharmcological mechanisms of regulation of exocytosis in posterior pituitary nerve terminals and pheochromocytoma 12 cells
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EAN 2940011728471
REGISTERED: 09/19/18
UPDATED: 12/14/18
Molecular and pharmcological mechanisms of regulation of exocytosis in posterior pituitary nerve terminals and pheochromocytoma 12 cells.
Posterior pituitary nerve terminals (PPNTs) and PC12 cells are useful model systems for the study of hormone release and synaptic exocytosis. Studying the molecular and pharmacological regulation of vesicle release in these systems will help understanding how the brain functions, and how drugs affect the brain. This thesis presents two studies using these systems: (i) the effects of phosphodiesterase 5 (PDE5) inhibitors on the excitability of PPNTs and peptide-hormone release, and (ii) the


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  • EAN bar code 2940011728471 ξ1 registered April 21 2016
  • Product category is Molecular-and-pharmcological-mechanisms-of-regulation-of-exocytosis-in-posterior-pituitary-nerve-terminals-and-pheochromocytoma-12-cells Zhenjie-Zhang Electronic Cell

Posterior pituitary nerve terminals (PPNTs) and PC12 cells are useful model systems for the study of hormone release and synaptic exocytosis. Studying the molecular and pharmacological regulation of vesicle release in these systems will help understanding how the brain functions, and how drugs affect the brain. This thesis presents two studies using these systems: (i) the effects of phosphodiesterase 5 (PDE5) inhibitors on the excitability of PPNTs and peptide-hormone release, and (ii) the regulatory role of syntaptotagmin IV in exocytosis. The latter study was performed in both PPNTs and PC12 cells.;Cyclic guanylyl monophosphate (cGMP) regulates neuroplasticity. By enhancing the Ca2 dependent large conductance K channel (BK channel) voltage dependently, cGMP increases posterior pituitary nerve terminal excitability. We show that blocking cGMP degradation with PDE5 inhibitors potentiates this effect. PDE5 inhibitors induced larger and longer BK current enhancement, and facilitated action potential firing during high frequency stimulation. In the whole posterior pituitary, PDE5 inhibition enhanced action potential propagation and oxytocin secretion. These results show that, besides the well studied vascular smooth muscle relaxation effect, PDE5 inhibitors also have an action on peptidergic nerve terminals.;Synaptotagmin is a family of proteins proposed to participate in the Ca2 triggering of exocytosis. The isoform synaptotagmin IV (syt IV) is an early immediate protein regulated by neural activity and development. Despite its involvement in learning and memory, this protein shows no Ca 2 sensitivity. Studies on the subcelluar localization and functions of syt IV yielded conflicting results. We found that syt IV is most abundant in the PPNTs compared with other brain regions examined. We studied the effects of syt IV knockout in this physiologically relevant environment, and showed that this protein localizes to both large dense core vesicles and microvesicles,


References
    ^ Molecular and pharmcological mechanisms of regulation of exocytosis in posterior pituitary nerve terminals and pheochromocytoma 12 cells. (revised Dec 2018)

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