Biomaterial Database

Degranulation in RBL-2H3 cells: regulation by calmodulin pathway. 2003

Masayuki Funaba, and Teruo Ikeda, and Matanobu Abe

Laboratory of Nutrition, Azabu University School of Veterinary Medicine, 1-17-71 Fuchinobe, Sagamihara 229-8501, Japan. funaba@azabu-u.ac.jp

Involvement of the calmodulin pathway in Ca2+-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 beta-hexosaminidase into the supernatant, although W-13 treatment alone slightly but significantly increased the release. Ca2+/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 beta-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 beta-hexosaminidase into the supernatant. Our results indicate that Ca2+/calmodulin, activated calmodulin, is indispensable for Ca2+-induced degranulation, and that within the calmodulin pathways, at least MLCK, CaMKs and calcineurin positively regulate the release of granules initiated by increasing cytosolic Ca2+ concentrations in RBL-2H3 cells.

UI	MeSH Term	Description	Entries
D009219	Myosin-Light-Chain Kinase	An enzyme that phosphorylates myosin light chains in the presence of ATP to yield myosin-light chain phosphate and ADP, and requires calcium and CALMODULIN. The 20-kDa light chain is phosphorylated more rapidly than any other acceptor, but light chains from other myosins and myosin itself can act as acceptors. The enzyme plays a central role in the regulation of smooth muscle contraction.	Myosin Kinase,Myosin LCK,Myosin Regulatory Light-Chain Kinase,Kinase, Myosin,Kinase, Myosin-Light-Chain,LCK, Myosin,Myosin Light Chain Kinase,Myosin Regulatory Light Chain Kinase
D009281	Naphthalenes	Two-ring crystalline hydrocarbons isolated from coal tar. They are used as intermediates in chemical synthesis, as insect repellents, fungicides, lubricants, preservatives, and, formerly, as topical antiseptics.
D010456	Peptides, Cyclic	Peptides whose amino acid residues are linked together forming a circular chain. Some of them are ANTI-INFECTIVE AGENTS; some are biosynthesized non-ribosomally (PEPTIDE BIOSYNTHESIS, NON-RIBOSOMAL).	Circular Peptide,Cyclic Peptide,Cyclic Peptides,Cyclopeptide,Orbitide,Circular Peptides,Cyclopeptides,Orbitides,Peptide, Circular,Peptide, Cyclic,Peptides, Circular
D002118	Calcium	A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.	Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002147	Calmodulin	A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels.	Calcium-Dependent Activator Protein,Calcium-Dependent Regulator,Bovine Activator Protein,Cyclic AMP-Phosphodiesterase Activator,Phosphodiesterase Activating Factor,Phosphodiesterase Activator Protein,Phosphodiesterase Protein Activator,Regulator, Calcium-Dependent,AMP-Phosphodiesterase Activator, Cyclic,Activating Factor, Phosphodiesterase,Activator Protein, Bovine,Activator Protein, Calcium-Dependent,Activator Protein, Phosphodiesterase,Activator, Cyclic AMP-Phosphodiesterase,Activator, Phosphodiesterase Protein,Calcium Dependent Activator Protein,Calcium Dependent Regulator,Cyclic AMP Phosphodiesterase Activator,Factor, Phosphodiesterase Activating,Protein Activator, Phosphodiesterase,Protein, Bovine Activator,Protein, Calcium-Dependent Activator,Protein, Phosphodiesterase Activator,Regulator, Calcium Dependent
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005786	Gene Expression Regulation	Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.	Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001381	Azepines	Seven membered heterocyclic rings containing a NITROGEN atom.	Hexamethyleneimines