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Title: The physiological role of endogenous nitric oxide in the magnocellular neurosecretory system
Author: Srisawat, Rungrudee
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2000
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The thesis examines the regulation of neuronal nitric oxide synthase (nNOS) mRNA expression in magnocellular neurosecretory neurones under physiological circumstances including pregnancy, hyperosmotic challenges and prolonged stimulation of the axons of the magnocellular neurones, and the functional role of nitric oxide (NO) in regulating oxytocin and vasopressin neuronal activities, and the release of oxytocin. The studies have included measurement of mRNA expression by in situ hybridization, in vivo electrophysiological studies combined with intrasupraoptic nucleus retrodialysis, Fos immunocytochemistry studies, and functional studies involving measurement of oxytocin secretion. Expression of nNOS mRNA in the magnocellular neurones in the supraoptic (SON) and paraventricular nuclei (PVN) has been confirmed to be regulated in response to chronic osmotic stimuli, suggesting an important involvement of NO in this situation. It has been demonstrated that an induction of this gene is not a rapid response since an increase of NOS gene expression in the magnocellular neurones in the SON and PVN has been found at 6 h after acute hypertonic saline intraperitoneal injection, but not at 4 h after injection. Neuronal activity of oxytocin and continuous firing vasopressin neurones in the SON was inhibited by local application of NO donor, and was increased by local administration of NOS inhibitor. Nitric oxide donor inhibited neuronal activity of phasic vasopressin neurones, while NOS inhibitor did not alter neuronal activities of these neurones. Blocking the central production of NOS by NOS inhibitor enhanced the expression of Fos in the magnocellular neurones in the SON and PVN following high doses, but not low doses of hypertonic saline. In addition, inhibition of NOS potentiated the release of oxytocin evoked by electrical stimulation of the axons of the magnocellular neurones. Furthermore, prolonged electrical stimulation of the axons of the magnocellular neurones for 2 h produced a down-regulation nNOS mRNA expression in the magnocellular neurones in the SON. Thus NO, generated in an activity-dependent manner, appears to act as a feedback inhibitor of oxytocin release at the cell bodies and the terminals of oxytocin neurones. However, although NOS expression is up-regulated in conditions of chronic demand of oxytocin, the present experiments indicate that this does not reflect a coupling of spike activity to increased NOS mRNA expression. In experiments in virgin rats, central administration of NO donor attenuated the release of oxytocin in response to acute intraperitoneal hypertonic saline and systemic administration of NOS inhibitor potentiated oxytocin release induced by acute intraperitoneal hypertonic saline but not cholecystokinin.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available