Document Detail


The calcium-sensing receptor couples to Galpha(s) and regulates PTHrP and ACTH secretion in pituitary cells.
MedLine Citation:
PMID:  20032198     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The calcium-sensing receptor (CaR or CASR as listed in the MGI Database) is a G protein-coupled receptor that binds and signals in response to extracellular calcium and other polycations. It is highly expressed on parathyroid and kidney cells, where it participates in the regulation of systemic calcium homeostasis. It is also expressed on many other cell types and is involved in a wide array of biological functions such as cell growth and differentiation, ion transport, and hormone secretion. It has been described to couple to several different G proteins including Galpha(i/0), Galpha(q/11), and Galpha(12/13). Recently, it has also been shown to stimulate cAMP production by coupling to Galpha(s) in immortalized or malignant breast cells. The CaR is expressed on cells in the anterior pituitary and had previously been described to stimulate cAMP production in these cells. In this report, we examined signaling from the CaR in murine pituitary corticotroph-derived, AtT-20 cells. We found that CaR activation led to the stimulation of cAMP production, and PTH-related protein (PTHrP or PTHLH as listed in the MGI Database) and ACTH secretion from these cells. Furthermore, manipulation of cAMP levels was able to modulate PTHrP and ACTH secretion independent of changes in extracellular calcium. Finally, we demonstrated that the CaR couples to Galpha(s) in AtT-20 cells. Therefore, in pituitary corticotroph-like cells, as in breast cancer cells, the CaR utilizes Galpha(s) and activates cAMP production to stimulate hormone secretion.
Authors:
Ramanaiah Mamillapalli; John Wysolmerski
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2009-12-23
Journal Detail:
Title:  The Journal of endocrinology     Volume:  204     ISSN:  1479-6805     ISO Abbreviation:  J. Endocrinol.     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-02-09     Completed Date:  2010-03-15     Revised Date:  2012-05-31    
Medline Journal Info:
Nlm Unique ID:  0375363     Medline TA:  J Endocrinol     Country:  England    
Other Details:
Languages:  eng     Pagination:  287-97     Citation Subset:  IM    
Affiliation:
Section of Endocrinology and Metabolism, Department of Internal Medicine, Yale University School of Medicine, TAC S131, New Haven, Connecticut 06520-8020, USA.
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MeSH Terms
Descriptor/Qualifier:
Adrenocorticotropic Hormone / secretion*
Animals
Cell Line
Cyclic AMP / metabolism
GTP-Binding Protein alpha Subunits, Gs / genetics,  metabolism*
Mice
Parathyroid Hormone-Related Protein / secretion*
Pituitary Gland / cytology,  secretion*
Receptors, Calcium-Sensing / genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
DK069542/DK/NIDDK NIH HHS; R01 CA153702-07/CA/NCI NIH HHS; R01 DK055501/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Parathyroid Hormone-Related Protein; 0/Receptors, Calcium-Sensing; 60-92-4/Cyclic AMP; 9002-60-2/Adrenocorticotropic Hormone; EC 3.6.5.1/GTP-Binding Protein alpha Subunits, Gs

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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