Protein phosphatase inhibitors induce the release of serotonin from rat basophilic leukemia cells (RBL-2H3).
Effects of okadaic acid (OA) and calyculin-A (CL-A), selective inhibitors of protein phosphatases 1 (PP1) and 2A (PP2A), on the release of serotonin from the rat basophilic leukemia cell line (RBL-2H3) were investigated. Both OA and CL-A induced the long-lasting release of serotonin in an extracellular Ca(2+)-independent manner. CL-A did not increase intracellular Ca2+ concentration in the fura-2-loaded cells. CL-A was 100-fold more potent than OA in inducing the release, suggesting that PP1 is a dominant protein phosphatase in regulating RBL-2H3 cells. The CL-A-induced release of serotonin was completely inhibited by the nonselective protein kinase inhibitors, staurosporine and K-252a. CL-A induced phosphorylation of several cellular proteins in RBL-2H3 cells, which could be inhibited by staurosporine. These findings suggest that the release of serotonin is subject to tonic, Ca(2+)-independent, inhibition by PP1 in RBL-2H3 cells.
Sakamoto
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N
Department of Pharmacology, Kobe University School of Medicine, Japan.
Shuntoh
H
H
Tanaka
C
C
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D004988:Ethers, Cyclic / Q000494:pharmacology; D015471:Leukemia, Basophilic, Acute / Q000378:metabolism*; D008387:Marine Toxins; D019319:Okadaic Acid; D010080:Oxazoles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D019311:Staurosporine; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000470:Alkaloids; D004988:Ethers, Cyclic; D008387:Marine Toxins; D010080:Oxazoles; D047428:Protein Kinase Inhibitors; D019319:Okadaic Acid; D012701:Serotonin; C059041:calyculin A; D010749:Phosphoprotein Phosphatases; D019311:Staurosporine; D002118:Calcium