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
✍ Scribed by Serge Poiraudeau; Michèle Lieberherr; Nathalie Kergosie; Marie-Thérèse Corvol
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 126 KB
- Volume
- 64
- Category
- Article
- ISSN
- 0730-2312
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✦ Synopsis
This study describes the mechanisms involved in the IGF-1 and IGF-2-induced increases in intracellular calcium concentration [Ca 21 ]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 21 ]i in a dose-dependent manner, with a plateau from 25 to 100 ng/ml for both IGF-1 and IGF-2and 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 21 ]i increase. 1) IGF-1 and insulin but not IGF-2 involved a Ca 21 influx through voltage-gated calcium channels: pretreatment of the cells by EGTA and verapamil diminished the IGF-1 or insulininduced [Ca 21 ]i but did not block the effect of IGF-2. 2) IGF-1, IGF-2, and insulin also induced a Ca 21 mobilization from the endoplasmic reticulum: phospholipase C (PLC) inhibitors, neomycin, or U-73122 partially blocked the intracellular [Ca 21 ]i increase induced by IGF-1 and insulin and totally inhibited the effect of IGF-2 . This Ca 21 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 21 spike and totally abolished the Ca 21 influx, but did not modify the effect of IGF-2. These results suggest that IGF-1 action on Ca 21 influx involves the IGF 1 receptor, while part of IGF-1 and all of IGF-2 Ca 21 mobilization do not implicate this receptor.