Document Detail

Involvement of phosphodiesterase-cGMP-PKG pathway in intracellular Ca2+ oscillations in pituitary GH3 cells.
MedLine Citation:
PMID:  10082977     Owner:  NLM     Status:  MEDLINE    
The present study investigates the potential role of the Ca2+-calmodulin-dependent type I phosphodiesterase (PDE)-cGMP-protein kinase G (PKG) pathway in spontaneous [Ca2+]i oscillations in GH3 cells using fura-2 single cell videoimaging. Vinpocetine (2.5-50 microM), a selective inhibitor of type I PDE, induced a concentration-dependent inhibition of spontaneous [Ca2+]i oscillations in these pituitary cells, and at the same time produced an increase of the intracellular cGMP content. The cell permeable cGMP analog N2,2'-O-dibutyryl-cGMP (dB-cGMP) (1 mM) caused a progressive reduction of the frequency and the amplitude of spontaneous [Ca2+]i oscillations when added to the medium. KT5823 (400 nM), a selective inhibitor of cGMP-dependent protein kinase (PKG), produced an increase of baseline [Ca2+]i and the disappearance of spontaneous [Ca2+]i oscillations. When KT5823 was added before vinpocetine, the PKG inhibitor counteracted the [Ca2+]i lowering effect of the cGMP catabolism inhibitor. Finally, the removal of extracellular Ca2+ or the blockade of L-type voltage-sensitive calcium channels (VSCC) by nimodipine produced a decrease of cytosolic cGMP levels. Collectively, the results of the present study suggest that spontaneous [Ca2+]i oscillations in GH3 cells may be regulated by the activity of type I PDE-cGMP-PKG pathway.
M Cataldi; A Secondo; A D'Alessio; F Sarnacchiaro; A M Colao; S Amoroso; G F Di Renzo; L Annunziato
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1449     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  1999 Mar 
Date Detail:
Created Date:  1999-04-27     Completed Date:  1999-04-27     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  186-93     Citation Subset:  IM    
Section of Pharmacology, Department of Neuroscience, School of Medicine, Federico II University of Naples, Via S. Pansini 5, 80131, Naples, Italy.
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MeSH Terms
Alkaloids / pharmacology
Calcium / metabolism
Cell Line
Cyclic AMP / metabolism
Cyclic GMP / metabolism*
Cyclic GMP-Dependent Protein Kinases
Cyclic Nucleotide Phosphodiesterases, Type 1
Dibutyryl Cyclic GMP / pharmacology
Enzyme Inhibitors / pharmacology
Indoles / pharmacology
Phosphoric Diester Hydrolases / metabolism*
Pituitary Gland / drug effects,  metabolism*
Protein Kinases / metabolism*
Pyrroles / pharmacology
Vinca Alkaloids / pharmacology
Reg. No./Substance:
0/Alkaloids; 0/Carbazoles; 0/Enzyme Inhibitors; 0/Indoles; 0/Pyrroles; 0/Vinca Alkaloids; 108068-98-0/KT 5720; 126643-37-6/KT 5823; 32266-35-6/Dibutyryl Cyclic GMP; 42971-12-0/vinpocetine; 60-92-4/Cyclic AMP; 7440-70-2/Calcium; 7665-99-8/Cyclic GMP; EC 2.7.-/Protein Kinases; EC GMP-Dependent Protein Kinases; EC 3.1.4.-/Phosphoric Diester Hydrolases; EC Nucleotide Phosphodiesterases, Type 1

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

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