The major aim of the proposed research is to define the cellular and molecular mechanism by which atrial natriuretic peptide (ANP) inhibits hormone stimulated aldosterone production from the adrenal glomerulosa cell. ANP, via a distinct surface receptor, inhibits the rate of aldosterone secretion stimulated by angiotensin II, extracellular potassium and adrenocorticotrophic hormone (ACTH). The stimulatory action of each of these agonists is mediated by the activation of cellular protein kinases. Using freshly isolated cells from calf adrenals, we will determine: 1) If ANP changes the cellular steady state concentration of cyclic nucleotides (increasing cGMP, decreasing cAMP) and/or alters the state of cyclic nucleotide turnover. 2) If these signals of ANP action, modulate receptor linked signal transduction events initiated by AII, ACTH, potassium. 3) If ANP prevents the activation of cellular protein kinases or enhances the stimulation of cellular phosphoprotein phosphatases. These studies will detail the biochemical mechanism of ANP action in the adrenal cell and as such, will help to realize the potential of ANP as a drug to be used in managing disorders of salt and water metabolism and in treating hypertension.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL036977-02
Application #
3352414
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Project Start
1987-07-01
Project End
1990-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
2
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Yale University
Department
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
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Yang, Tingting; Zhang, Hai-Liang; Liang, Qingnan et al. (2016) Small-Conductance Ca2+-Activated Potassium Channels Negatively Regulate Aldosterone Secretion in Human Adrenocortical Cells. Hypertension 68:785-95
Manichaikul, Ani; Rich, Stephen S; Allison, Matthew A et al. (2016) KCNK3 Variants Are Associated With Hyperaldosteronism and Hypertension. Hypertension 68:356-64
Orestes, Peihan; Osuru, Hari Prasad; McIntire, William E et al. (2013) Reversal of neuropathic pain in diabetes by targeting glycosylation of Ca(V)3.2 T-type calcium channels. Diabetes 62:3828-38
Freedman, Bethany D; Kempna, Petra Bukovac; Carlone, Diana L et al. (2013) Adrenocortical zonation results from lineage conversion of differentiated zona glomerulosa cells. Dev Cell 26:666-673
Hu, Changlong; Rusin, Craig G; Tan, Zhiyong et al. (2012) Zona glomerulosa cells of the mouse adrenal cortex are intrinsic electrical oscillators. J Clin Invest 122:2046-53
Guagliardo, Nick A; Yao, Junlan; Hu, Changlong et al. (2012) TASK-3 channel deletion in mice recapitulates low-renin essential hypertension. Hypertension 59:999-1005
Guagliardo, Nick A; Yao, Junlan; Hu, Changlong et al. (2012) Minireview: aldosterone biosynthesis: electrically gated for our protection. Endocrinology 153:3579-86
Guagliardo, Nick A; Yao, Junlan; Bayliss, Douglas A et al. (2011) TASK channels are not required to mount an aldosterone secretory response to metabolic acidosis in mice. Mol Cell Endocrinol 336:47-52
Hu, Changlong; Depuy, Seth D; Yao, Junlan et al. (2009) Protein kinase A activity controls the regulation of T-type CaV3.2 channels by Gbetagamma dimers. J Biol Chem 284:7465-73

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