Cellular calcium has a pivotal regulatory role in many aspects of: 1) normal physiology, such as hormone secretion, control of other intracellular messengers and modulation of cancer-promoting oncogenes; and 2) human disease (calcium is a pathogenic factor in the neuronal damage due to stroke, epilepsy and hypoglycemia). With hormone secretion from rat anterior pituitary cells as the model system, the broad objective of this program is to learn how normal cells control calcium ion movements and calcium concentration and compare this knowledge with observations in cancer cells where calcium-dependent activities are abnormal. Endogenous hypothalamic hormones or selected pharmacologic agents will be applied to cultured normal or neoplastic anterior pituitary cells to perturb the intrinsic systems modulating calcium flux as the cell executes its biological role of hormone secretion. The intracellular calcium concentrations will be measured with an intracellular fluorescent probe, Indo-1, during perifusion of the pituitary cells to allow concomitant analysis of the hormone secretory rate. These investigations will shed light on the normal mechanisms governing calcium ion flux and the alterations that confer neoplastic properties upon certain cells. The experimental procedures required to complete this project are established and the preliminary work demonstrates feasibility.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA038228-06
Application #
2089533
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1985-12-01
Project End
1996-05-31
Budget Start
1994-06-01
Budget End
1995-05-31
Support Year
6
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Virginia
Department
Neurology
Type
Schools of Medicine
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
Login, I S; Pal, S N; Adams, D T et al. (1998) Muscimol increases acetylcholine release by directly stimulating adult striatal cholinergic interneurons. Brain Res 779:33-40
Login, I S (1997) Carbachol inhibits basal and forskolin-evoked adult rat striatal acetylcholine release. Neuroreport 8:1863-6
Login, I S (1997) D2 dopamine receptor activation inhibits basal and forskolin-evoked acetylcholine release from dissociated striatal cholinergic interneurons. Brain Res 749:147-51
Login, I S; Harrison, M B (1996) A D1 dopamine agonist stimulates acetylcholine release from dissociated striatal cholinergic neurons. Brain Res 727:162-8
Login, I S; Hewlett, E L (1996) Adenylate cyclase in striatal cholinergic interneurons regulates acetylcholine release. Brain Res 735:330-4
Login, I S; Borland, K; Harrison, M B et al. (1995) Acetylcholine release from dissociated striatal cells. Brain Res 697:271-5
Login, I S; Borland, K; Harrison, M B (1995) Acute dopamine depletion potentiates independent stimulatory and inhibitory D1 DA receptor-mediated control of striatal acetylcholine release in vitro. Brain Res 681:209-12
Goger, M J; Login, I S; Fernandez, E J et al. (1994) 31P NMR investigation of energy metabolism in perifused MMQ cells. Magn Reson Med 32:584-91
Login, I S; Judd, A M; Kuan, S I et al. (1991) Role of calcium in dopaminergic regulation of TRH- and angiotensin II-stimulated prolactin release. Am J Physiol 260:E553-60
Login, I S; Pancrazio, J J; Kim, Y I (1990) Dopamine enhances a voltage-dependent transient K+ current in the MMQ cell, a clonal pituitary line expressing functional D2 dopamine receptors. Brain Res 506:331-4

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