Agonist-induced down-regulation of human 5-HT1A and 5-HT2 receptors in Swiss 3T3 cells.
We have used single cell clones of Swiss 3T3 cells transfected with genes for the human 5-HT1A or 5-HT2 receptor to study down-regulation and desensitization. After pre-incubation of the cells with serotonin agonists, a time-dependent decrease in [3H]8-hydroxy-2-(di-n-propylamino) tetralin or [3H]ketanserin binding was observed. The pertussis toxin sensitive, 5-HT mediated inhibition of forskolin-stimulated cAMP accumulation in 5-HT1A receptor transfected cells was diminished by 68% after a 2 h pre-incubation of the cells with 10 microM 5-HT. The pertussis toxin insensitive, 5-HT mediated PI turnover in 5-HT2 receptor transfected cells was decreased by 65% after pre-treatment. While this decrease was paralleled by a decreased potency of 5-HT to stimulate PI turnover, in 5-HT1A cells the potency of 5-HT to inhibit cAMP formation was comparable to control values. The down-regulation and desensitization of the 5-HT2 receptor can be explained by phosphorylation via activated PKC. In contrast, the attenuation of the 5-HT1A receptor-coupled inhibition of cAMP accumulation has to occur by an alternative, as yet unknown, molecular mechanism.
van Huizen
F
F
Department of Neuropharmacology, Organon International B.V., Oss, The Netherlands.
Bansse
M T
MT
Stam
N J
NJ
D016475:3T3 Cells; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects*; D006801:Humans; D006868:Hydrolysis; D007650:Ketanserin / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D008815:Mice, Inbred Strains; D037342:Pertussis Toxin; D010716:Phosphatidylinositols / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D010716:Phosphatidylinositols; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D007650:Ketanserin; D000242:Cyclic AMP; D037342:Pertussis Toxin