Document Detail

Down-regulation of PTH-PTHrP receptor of heart in CRF: role of [Ca2+]i.
MedLine Citation:
PMID:  7783417     Owner:  NLM     Status:  MEDLINE    
The mRNA of PTH-PTHrP receptor in the kidney and liver of CRF rats is down-regulated. It is not known whether this is a generalized phenomenon and the signals that mediate such down-regulation are not evident. Excess PTH in CRF induces a rise in basal levels of cytosolic calcium ([Ca2+]i), and the high [Ca2+]i is implicated in the genesis of cell dysfunction in CRF. Therefore, it is reasonable to propose that the PTH-induced rise in [Ca2+]i provides a negative feedback control system for the down-regulation of the mRNA of the PTH-PTHrP in order to protect the cells from the harmful effects of progressive rise in blood levels of PTH in CRF. The heart contains the mRNA for this receptor and it is a target organ for PTH action. We examined whether the message of the PTH-PTHrP receptor is down-regulated in the heart of CRF animals and evaluated the role of [Ca2+]i in this process. The expression of the mRNA of the PTH-PTHrP was significantly reduced in the heart of CRF rats as compared to normal animals. Also, the CRF rats had elevated blood levels of PTH and high [Ca2+]i of cardiac myocytes. The parathyroidectomy of CRF rats prevented the rise in blood PTH levels and normalized [Ca2+]i of cardiac myocytes and returned the mRNA of their PTH-PTHrP receptor towards normal levels. The treatment of CRF rats with verapamil normalized [Ca2+]i of cardiac myocytes and returned the mRNA of their PTH-PTHrP receptor towards normal levels, despite marked elevation of blood levels of PTH.(ABSTRACT TRUNCATED AT 250 WORDS)
M Smogorzewski; J Tian; S G Massry
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Kidney international     Volume:  47     ISSN:  0085-2538     ISO Abbreviation:  Kidney Int.     Publication Date:  1995 Apr 
Date Detail:
Created Date:  1995-07-17     Completed Date:  1995-07-17     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0323470     Medline TA:  Kidney Int     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1182-6     Citation Subset:  IM    
Division of Nephrology, University of Southern California School of Medicine, Los Angeles, USA.
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MeSH Terms
Actins / drug effects,  metabolism
Analysis of Variance
Blotting, Northern
Calcium / metabolism*
Down-Regulation / drug effects,  physiology*
Kidney Failure, Chronic / metabolism*,  pathology
Myocardium / metabolism*,  pathology
Parathyroid Glands / drug effects,  metabolism
Parathyroid Hormone / blood
RNA, Messenger / metabolism*
Rats, Sprague-Dawley
Receptor, Parathyroid Hormone, Type 1
Receptors, Parathyroid Hormone / drug effects,  metabolism*
Spectrophotometry, Atomic
Verapamil / pharmacology
Grant Support
Reg. No./Substance:
0/Actins; 0/Parathyroid Hormone; 0/RNA, Messenger; 0/Receptor, Parathyroid Hormone, Type 1; 0/Receptors, Parathyroid Hormone; 52-53-9/Verapamil; 7440-70-2/Calcium

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