Degranulation in RBL-2H3 cells: regulation by calmodulin pathway

✍ Scribed by Masayuki Funaba; Teruo Ikeda; Matanobu Abe

• Book ID: 104375308
• Publisher: Elsevier Science
• Year: 2003
• Tongue: English
• Weight: 216 KB
• Volume: 27
• Category: Article
• ISSN: 1065-6995
• DOI: 10.1016/s1065-6995(03)00177-x

✦ Synopsis

Abstract

Involvement of the calmodulin pathway in Ca^2+^‐induced degranulation was evaluated in RBL‐2H3 mast cells. Pretreatment of RBL‐2H3 cells with a calmodulin antagonist, W‐13, blocked ionomycin‐dependent release of β‐hexosaminidase into the supernatant, although W‐13 treatment alone slightly but significantly increased the release. Ca^2+^/calmodulin activates various protein kinases and phosphatases including myosin‐light chain kinase (MLCK), calmodulin‐dependent protein kinases (CaMKs), and calcineurin. When RBL‐2H3 cells were pretreated with a MLCK inhibitor, ML‐7, or a CaMKs inhibitor, KN‐93, the ionomycin‐dependent release of β‐hexosaminidase into the supernatant was inhibited. In addition, pretreatment with calcineurin inhibitors, cyclosporin A and FR901725, resulted in blockage of the ionomycin‐dependent release of β‐hexosaminidase into the supernatant. Our results indicate that Ca^2+^/calmodulin, activated calmodulin, is indispensable for Ca^2+^‐induced degranulation, and that within the calmodulin pathways, at least MLCK, CaMKs and calcineurin positively regulate the release of granules initiated by increasing cytosolic Ca^2+^concentrations in RBL‐2H3 cells.