Serotonin-induced 5-HT1A receptor desensitization in C6BU-1 glioma cells transfected with 5-HT1A receptor gene.
In this study, it has been clearly demonstrated that a selective 5-hydroxytryptamine (5-HT)1A agonist, 8-OH-2-(di-n-propylamino)-tetraline (8-OH-DPAT, 1 microM) significantly inhibited forskolin (10 microM)-stimulated cyclic AMP (cAMP) accumulation in the C6BU-1 cells transfected with 5-HT1A receptor gene. Further, this 8-OH-DPAT-induced inhibition of forskolin-stimulated activity was significantly attenuated after pre-exposure to 5-HT (10 microM) for 12 h. Spiperone (10 microM), a 5-HT1A and 5-HT2A antagonist, prevented 5-HT-induced desensitization of 5-HT1A receptor, but a selective 5-HT2A receptor antagonist, ketanserin, did not. In addition, pre-exposure to a selective 5-HT2A agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI, 10 microM), for 24 h did not alter the inhibitory effect of 8-OH-DPAT on forskolin-stimulated cAMP accumulation in these transfected cells, suggesting that prolonged exposure to 5-HT induced 5-HT1A receptor desensitization, mediated by 5-HT1A receptor but not 5-HT2A receptors.
Saitoh
K
K
Department of Mental Disorder Research, National Institute of Neuroscience, N.C.N.P., Tokyo, Japan.
Mikuni
M
M
Ikeda
M
M
Yamazaki
C
C
Tomita
U
U
Takahashi
K
K
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005910:Glioma / Q000378:metabolism*; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000502:physiology*; D013997:Time Factors
D011985:Receptors, Serotonin; D005576:Colforsin; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000242:Cyclic AMP