Homologous desensitization of serotonin 5-HT2 receptor-stimulated intracellular calcium mobilization in C6BU-1 glioma cells via a mechanism involving a calmodulin pathway.
Serotonin 5-HT2 receptor-mediated intracellular Ca2+ mobilization was investigated in rat glioma C6BU-1 cells. The receptors became desensitized after previous exposure to 5-HT in a time- and concentration-dependent manner. The desensitization of 5-HT2 receptor-mediated intracellular signaling appeared to be homologous because previous exposure to 5-HT did not alter the response to other transmitters such as thrombin or isoproterenol and because previous exposure to thrombin or isoproterenol did not diminish the response to 5-HT. The desensitization induced by pretreatment with 5-HT was potently prevented by the naphthalenesulfonamide derivative W-7, a calmodulin antagonist, when it was cosupplied with 5-HT. Furthermore, the preventive effect of W-7 was greater than that of W-5, a weak analogue of W-7, and than that of H-7, a nonselective inhibitor of protein kinases. These results suggest that 5-HT2 receptor-mediated Ca2+ mobilization can be desensitized homologously after prolonged exposure to 5-HT in a calmodulin-dependent manner in rat glioma C6BU-1 cells.
Kagaya
A
A
Division of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
Mikuni
M
M
Muraoka
S
S
Saitoh
K
K
Ogawa
T
T
Shinno
H
H
Yamawaki
S
S
Takahashi
K
K
D000818:Animals; D001692:Biological Transport; D002147:Calmodulin / Q000378:metabolism*; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D007425:Intracellular Membranes / Q000378:metabolism*; D011493:Protein Kinase C / Q000494:pharmacology; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D002147:Calmodulin; D011985:Receptors, Serotonin; D013449:Sulfonamides; D012701:Serotonin; C051353:naphthalenesulfonamide; D011493:Protein Kinase C