Abstract

Two years of support for this project will allow us to perform the experiments proposed in Aims 3 and 4 of the original application. We have been able to complete the bulk of Aims 1 and 2 with support from the American Heart Assoc. This supported our hypothesis that simultaneous exposure of supraoptic neurons (SON) to ATP and phenylephrine induces a shift to non-desensitizing ionotropic purinergic receptor subtypes that allow ATP to sustain vasopressin (VP) release for hours. This work has been submitted for publication. The AHA grant does not provide support for Aims 3 and 4 which are crucial to understanding the mechanism by which norepinephrine can induce the shift in purinergic receptor subtype:
Aim 3 is focused on identifying the a1-adrenergic receptor subtype activated by phenylephrine in SON and Aim 4 will identify the signal cascades activated by phenylephrine in SON. Identifying the a1-R signal cascade is critical to understanding why ATP activation of metabotropic purinergic receptors does not induce the same effect as phenylephrine. The ability of phenylephrine to induce sustained responses to ATP is important, because it provides a mechanism for homeostatic CNS regulatory systems to mount extended responses in order, for example, to restore blood volume following hemorrhage or for sustained arousal.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS027975-18A2
Application #
7524172
Study Section
Neuroendocrinology, Neuroimmunology, and Behavior Study Section (NNB)
Program Officer
Mitler, Merrill
Project Start
2009-07-01
Project End
2011-06-30
Budget Start
2009-07-01
Budget End
2010-06-30
Support Year
18
Fiscal Year
2009
Total Cost
$364,149
Indirect Cost

  Institution

Name
University of Colorado Denver
Department
Physiology
Type
Schools of Medicine
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045

  Publications

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

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