Serotonin induces an increase in D-myo-inositol (1,4,5)-trisphosphate 3-kinase activity in rat brainstem slices

Serotonin robustly potentiated the activity of the InsP(3) 3-kinase in rat brainstem slices. This potentiation was mediated through activation of 5-HT2 receptors since it was only retrieved with the selective 5-HT2 agonist DOI but not with the 5-HT1A agonist 8OHDPAT. The enhancement of the InsP(3) 3-kinase activity by serotonin is positively modulated by pretreatment of the slices with the phosphatase inhibitor okadaic acid. Moreover, the specific CaMKII antagonists KN-62 and KN-93 dramatically reduced the serotonin-evoked increase in the InsP(3) 3-kinase activity. It is thus concluded that InsP(3) 3kinase up-regulation occurs through activation of PLC-coupled serotoninergic receptors and requires the phosphorylation of the enzyme by the ubiquitous multimeric protein kinase CaMKII. (C) 1998 Published by Elsevier Science Ireland Ltd. All rights reserved.