The goal of this project is to understand the mechanisms which allow neurons to integrate diverse regulatory signals into functional responses. Vasopressin (VP) neurons of the hypothalamo-neurohypophseal system (HNS) will serve as the model neuron in these studies, because they respond to wide ranging afferents, and integrate this information into a physiologically appropriate rate of hormone secretion. In addition to responding to afferents from the brainstem, hypothalamus, and forebrain that utilize an array of neurotransmitters and neuropeptides, the VP neurons also respond to non-synaptic signals such as osmolality of the extracellular fluid and steroid hormones. The proposed experiments will address two hypotheses: 1) Agonists of ionotropic receptors represent the primary regulators of VP neurons, and the action of these neurotransmitters is modulated via agonists of G-protein linked receptors and steroid hormones. 2) G-protein linked agonists also regulate VP gene expression and/or mRNA stability independent of ionotropic receptor agonists.
The specific aims of the proposal are: 1. To evaluate the role of excitatory amino acids (EAA) in the regulation of VP release and VPmRNA. 2. To evaluate the relationship between EAA ionotropic receptor agonists and G-protein linked receptor agonists. 3. To evaluate modulation of EAA stimulation by steroid hormones. 4. To evaluate the autoregulation of neurohypophyseal hormone secretion by VP and OT. Explants of the HNS will be used in all of the proposed experiments. These explants respond to a slow increase in osmolality with a sustained increase in VP release and an increase in VPmRNA content. VP release from these explants is also stimulated by EAA agonists, ATP and GABAergic antagonists. Where appropriate, HNS explants from mice strains with null mutations in specific genes of interest to this proposal will be used.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS027975-10
Application #
6187235
Study Section
Special Emphasis Panel (ZRG1-IFCN-2 (01))
Program Officer
Kitt, Cheryl A
Project Start
1991-05-01
Project End
2003-06-30
Budget Start
2000-07-01
Budget End
2001-06-30
Support Year
10
Fiscal Year
2000
Total Cost
$227,798
Indirect Cost
Name
Rosalind Franklin University
Department
Physiology
Type
Schools of Medicine
DUNS #
069501252
City
North Chicago
State
IL
Country
United States
Zip Code
60064
Sladek, Celia D; Johnson, Alan Kim (2013) Integration of thermal and osmotic regulation of water homeostasis: the role of TRPV channels. Am J Physiol Regul Integr Comp Physiol 305:R669-78
Sladek, C D; Song, Z (2012) Diverse roles of G-protein coupled receptors in the regulation of neurohypophyseal hormone secretion. J Neuroendocrinol 24:554-65
Doherty, Faye C; Schaack, Jerome B; Sladek, Celia D (2011) Comparison of the efficacy of four viral vectors for transducing hypothalamic magnocellular neurosecretory neurons in the rat supraoptic nucleus. J Neurosci Methods 197:238-48
Doherty, Faye C; Sladek, Celia D (2011) NMDA receptor subunit expression in the supraoptic nucleus of adult rats: dominance of NR2B and NR2D. Brain Res 1388:89-99
Sladek, Celia D; Song, Zhilin (2008) Regulation of vasopressin release by co-released neurotransmitters: mechanisms of purinergic and adrenergic synergism. Prog Brain Res 170:93-107
Sladek, Celia D; Somponpun, Suwit J (2008) Estrogen receptors: their roles in regulation of vasopressin release for maintenance of fluid and electrolyte homeostasis. Front Neuroendocrinol 29:114-27
Song, Zhilin; Vijayaraghavan, Sukumar; Sladek, Celia D (2007) ATP increases intracellular calcium in supraoptic neurons by activation of both P2X and P2Y purinergic receptors. Am J Physiol Regul Integr Comp Physiol 292:R423-31
Somponpun, S J (2007) Neuroendocrine regulation of fluid and electrolyte balance by ovarian steroids: contributions from central oestrogen receptors. J Neuroendocrinol 19:809-18
Song, Z; Sladek, C D (2006) Site of ATP and phenylephrine synergistic stimulation of vasopressin release from the hypothalamo-neurohypophyseal system. J Neuroendocrinol 18:266-72
Song, Zhilin; Vijayaraghavan, Sukumar; Sladek, Celia D (2006) Simultaneous exposure to ATP and phenylephrine induces a sustained elevation in the intracellular calcium concentration in supraoptic neurons. Am J Physiol Regul Integr Comp Physiol 291:R37-45

Showing the most recent 10 out of 38 publications