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 InsP3 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 InsP3 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 InsP3 3-kinase activity. It is thus concluded that InsP3 3-kinase up-regulation occurs through activation of PLC-coupled serotoninergic receptors and requires the phosphorylation of the enzyme by the ubiquitous multimeric protein kinase CaMKII.
Collin
T
T
Laboratoire de Neurobiologie Cellulaire et Intégrée du Contrôle de la Respiration, CNRS-EP 1592, Université de Picardie Jules Verne, Faculté de Médecine, Amiens, France. tc-lnc@u-picardie.fr
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D001933:Brain Stem / Q000187:drug effects* / Q000201:enzymology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007215:Indophenol / Q000031:analogs & derivatives / Q000494:pharmacology; D019319:Okadaic Acid / Q000494:pharmacology; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D051381:Rats; D011985:Receptors, Serotonin / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D000096926:Benzenesulfonamides
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D001596:Benzylamines; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D004791:Enzyme Inhibitors; D007215:Indophenol; D019319:Okadaic Acid; D010744:Phosphoric Monoester Hydrolases; D017853:Phosphotransferases (Alcohol Group Acceptor); D011985:Receptors, Serotonin; D012701:Serotonin; D017366:Serotonin Receptor Agonists; D013449:Sulfonamides; C113896:dimethoxy-4-indophenyl-2-aminopropane; C072105:KN 93; D000096926:Benzenesulfonamides; C063302:KN 62; C051038:Inositol 1,4,5-trisphosphate 3-kinase