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Different mechanisms are involved in intracellular calcium increase by insulin‐like growth factors 1 and 2 in articular chondrocytes: Voltage‐gated calcium channels, and/or phospholipase C coupled to a pertussis‐sensitive G‐protein
Author(s) -
Poiraudeau Serge,
Lieberherr Michèle,
Kergosie Nathalie,
Corvol MarieThérèse
Publication year - 1997
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(19970301)64:3<414::aid-jcb8>3.0.co;2-y
Subject(s) - pertussis toxin , endocrinology , medicine , phospholipase c , calcium in biology , intracellular , calcium , endoplasmic reticulum , insulin , insulin like growth factor , egta , biology , voltage dependent calcium channel , receptor , verapamil , chemistry , microbiology and biotechnology , growth factor , g protein
This study describes the mechanisms involved in the IGF‐1 and IGF‐2‐induced increases in intracellular calcium concentration [Ca 2+ ]i in cultured chondrocytes and the involvement of type 1 IGF receptors. It shows that IGF‐1, IGF‐2, and insulin increased the cytosolic free calcium concentration [Ca 2+ ]i in a dose‐dependent manner, with a plateau from 25 to 100 ng/ml for both IGF‐1 and IGF‐2 and from 1 to 2 μg/ml for insulin. The effect of IGF‐1 was twice as great as the one of IGF‐2, and the effect of insulin was 40% lower than IGF‐1 effect. Two different mechanisms are involved in the intracellular [Ca 2+ ]i increase. 1) IGF‐1 and insulin but not IGF‐2 involved a Ca 2+ influx through voltage‐gated calcium channels: pretreatment of the cells by EGTA and verapamil diminished the IGF‐1 or insulin‐induced[Ca 2+ ]i but did not block the effect of IGF‐2.2)IGF‐1, IGF‐2, and insulin also induced a Ca 2+ mobilization from the endoplasmic reticulum: phospholipase C (PLC) inhihitors, neomycin, or U‐73122 partially blocked the intracellular [Ca 2+ ]i increase induced by IGF‐1 and insulin and totally inhibited the effect of IGF‐2. This Ca 2+ mobilization was pertussis toxin (PTX) dependent, suggesting an activation of a PLC coupled to a PTX‐sensitive G‐protein. Lastly, preincubation of the cells with IGF 1 receptor antibodies diminished the IGF‐1‐induced Ca 2+ spike and totally abolished the Ca 2+ influx, but did not modify the effect of IGF‐2. These results suggest that IGF‐1 action on Ca 2+ influx involves the IGF 1 receptor, while part of IGF‐1 and all of IGF‐2 Ca 2+ mobilization do not implicate this receptor. J. Cell. Biochem. 64:414–422. © 1997 Wiley‐Liss, Inc.