Document Detail

Desensitization of calcium messenger system in parathyroid hormone-stimulated opossum kidney cells.
MedLine Citation:
PMID:  8392807     Owner:  NLM     Status:  MEDLINE    
We have studied the desensitization of the calcium message system to parathyroid hormone (PTH) by monitoring intracellular calcium concentration ([Ca2+]i) in an opossum kidney cell line (OKP). PTH (10(-7) M) caused a transient increase in [Ca2+]i, with an average peak height of 48.7 +/- 4.7% above baseline (n = 32). Cells stimulated with either 10(-7) or 10(-8) M PTH did not respond to a second challenge with a maximal dose (10(-7) M) of the hormone, whereas lower concentrations of PTH (10(-9) M and 10(-10) M) only partially desensitized the cells, since a [Ca2+]i transient of smaller amplitude (12.7 +/- 2.1 and 40.6 +/- 6.2% above baseline, respectively) was observed with a second stimulation. Desensitization developed within 5 min of initial hormone exposure, when PTH receptor binding was not significantly decreased. Maximal reduction of PTH binding sites (37.0 +/- 1.4%) was achieved only after 2 h. Partial desensitization was reproduced by 10(-9) M phorbol 12-myristate 13-acetate (PMA) but not by dibutyryladenosine 3',5'-cyclic monophosphate, and it was blocked by staurosporine. However, staurosporine had no effect on the complete desensitization induced by high doses of PTH. At 10(-9) M, PTH also caused a time-dependent desensitization of the adenosine 3',5'-cyclic monophosphate (cAMP) response, with maximal inhibition achieved after 2 h. PMA also decreased the cAMP response to PTH, but its inhibitory effect was less potent than that of 10(-9) M PTH. Therefore PTH induces a dose-dependent homologous desensitization of the Ca2+ message system in OKP cells, independent of receptor occupancy.(ABSTRACT TRUNCATED AT 250 WORDS)
A Fujimori; A Miyauchi; K A Hruska; K J Martin; L V Avioli; R Civitelli
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The American journal of physiology     Volume:  264     ISSN:  0002-9513     ISO Abbreviation:  Am. J. Physiol.     Publication Date:  1993 Jun 
Date Detail:
Created Date:  1993-08-13     Completed Date:  1993-08-13     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0370511     Medline TA:  Am J Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  E918-24     Citation Subset:  IM    
Division of Bone and Mineral Diseases, Jewish Hospital of St. Louis, Washington University Medical Center, St. Louis, Missouri.
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MeSH Terms
Alkaloids / pharmacology
Calcium / metabolism,  physiology*
Clone Cells
Cyclic AMP / metabolism
Dose-Response Relationship, Drug
Intracellular Membranes / metabolism
Kidney / cytology,  drug effects*,  physiology*
Osmolar Concentration
Parathyroid Hormone / metabolism,  pharmacology*
Protein Kinase C / antagonists & inhibitors
Second Messenger Systems*
Tetradecanoylphorbol Acetate / pharmacology
Grant Support
Reg. No./Substance:
0/Alkaloids; 0/Parathyroid Hormone; 16561-29-8/Tetradecanoylphorbol Acetate; 60-92-4/Cyclic AMP; 62996-74-1/Staurosporine; 7440-70-2/Calcium; EC Kinase C

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