TY - JOUR
T1 - Involvement of phosphodiesterase-cGMP-PKG pathway in intracellular Ca2+ oscillations in pituitary GH3 cells
AU - Cataldi, M.
AU - Secondo, A.
AU - D'Alessio, A.
AU - Sarnacchiaro, F.
AU - Colao, A. M.
AU - Amoroso, S.
AU - Di Renzo, G. F.
AU - Annunziato, L.
PY - 1999/3/8
Y1 - 1999/3/8
N2 - 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 μM), 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. Copyright (C) 1999.
AB - 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 μM), 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. Copyright (C) 1999.
KW - cGMP
KW - Intracellular Ca concentration
KW - Oscillation
KW - Phosphodiesterase
KW - Pituitary
KW - Protein kinase G
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U2 - 10.1016/S0167-4889(99)00013-0
DO - 10.1016/S0167-4889(99)00013-0
M3 - Article
C2 - 10082977
AN - SCOPUS:0033033092
VL - 1449
SP - 186
EP - 193
JO - Biochimica et Biophysica Acta - Molecular Cell Research
JF - Biochimica et Biophysica Acta - Molecular Cell Research
SN - 0167-4889
IS - 2
ER -