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Celia D. Sladek, Professor

Ph.D. (1970) Northwestern University Medical School



Department of Physiology & Biophysics

Campus Box 8307
RC1-North, P18-7127

Phone: 303-724-4526

Celia.Sladek@UCDenver.edu

The major focus of my laboratory has been understanding the mechanisms that regulate gene expression and secretion of the hormones, vasopressin (also called antidiuretic hormone) and oxytocin. They are produced by neurons in the hypothalamus, are released from the neurohypophysis into the blood stream, and regulate respectively the two functions that are hallmarks of mammalian physiology: formation of a concentrated urine by the kidneys and mammary gland function.

A unique aspect of this program has been the development and extensive use of an organ-cultured explant preparation of the hypothalamo-neurohypophyseal system that allows study of hormone release and gene expression in an in vitro system. The explant also includes osmoreceptive elements critical for the regulation of vasopressin secretion. Thus, it has significantly advanced our understanding of the mechanisms underlying fluid and electrolyte disturbances observed clinically (e.g. in congestive heart failure, schizophrenia, and aging). These explants are currently being used to evaluate the role of neurotransmitters and steroid hormones in the regulation of vasopressin and oxytocin secretion.

neuron

 

Dispersed primary hypothalamic cultures are also being used to investigate the signals important in regulation of oxytocin and vasopressin gene expression. An example of a neuron from these cultures is shown. It could either be an oxytocin neuron, as oxytocin is known as the ‘love hormone’ or it could be a vasopressin neuron reflecting the role of vasopressin in regulating cardiovascular function. Other techniques employed in the laboratory include immunocytochemistry, in situ hybridization, image analysis, radioimmunoassay, and mRNA extraction, quantification, and characterization using Northern analysis and RNA protection assays.

Gomes, D.A.*, Z. Song*, W. Stevens, and C.D. Sladek. Switch from desensitizing to non-desensitizing P2X receptors mediates sustained stimulation of vasopressin release. Am J Physiol Regul Integr Comp Physiology, July, 2009. *Contributed equally to this work. [Epub ahead of print: http://0-ajpregu.physiology.org.impulse.ucdenver.edu/cgi/content/abstract/00358.2009v1]

Sladek, C.D. and Z. Song. Regulation of vasopressin release by co-released neurotransmitters: Mechanisms of purinergic and adrenergic synergism. Progress in Brain Research (Advances in Vasopressin and Oxytocin – From Gene to Behavior; I.D. Neumann and R. Landgraf, eds) 170:93-107, 2008.

Song, Z., S. Vijayaraghavan, and C.D. Sladek. ATP increases intracellular calcium in supraoptic neurons by activation of both P2X and P2Y purinergic receptors. Am J Physiol Regul Integr Comp Physiol. 292(1):R423-31, 2007.

Song, Z., S. Vijayaraghavan, and C.D. Sladek. Simultaneous exposure to ATP and Phenylephrine induces a sustained elevation in the intracellular calcium concentration in supraoptic neurons. Am. J. Physiol. Reg. Integrative Physiol. 291:R37-R45, 2006.

Urban, J.H., R. Leitermann, M.R. de Joseph, S.J. Somponpun, M. Woleck, and C. D. Sladek. Influence of dehydration on the expression of
neuropeptide Y Y1 receptors in hypothalamic magnocellular neurons. Endocrinology, 2006 May 25

Song, Z., S. Vijayaraghavan, and C.D. Sladek. ATP increases intracellular calcium in supraoptic neurons by activation of both P2X and
P2Y purinergic receptors. Am. J. Physiol. Reg. Integrative Physiol., September, 2006

Sladek CD. Vasopressin response to osmotic and hemodynamic stress: neurotransmitter involvement. Stress. 2004 Jun;7(2):85-90.

Somponpun SJ, Sladek CD. Depletion of oestrogen receptor-beta expression in magnocellular arginine vasopressin neurones by hypovolaemia and dehydration. J Neuroendocrinol. 2004 Jun;16(6):544-9.


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