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• W2141175006 abstract "The serotonin (5-HT)2A and 5-HT2C receptors share a high degree of sequence homology and have very similar pharmacological profiles. Although it is generally believed that the cellular signal transduction mechanisms activated by these receptors are indistinguishable, recent data suggest significant differences in their signaling cascades. In this study we explored differences in the characteristics and mechanisms of rapid desensitization between the 5-HT2A and 5-HT2C receptor systems. For both receptor systems, pretreatment with 5-HT reduced the ability of a maximal concentration of 5-HT to stimulate phospholipase C-mediated inositol phosphate accumulation by about 65%, although the 5-HT2C receptor system was more sensitive to the desensitizing stimulus. Differences in the concentration dependence of the rate constant for desensitization (k(des)) suggested different mechanisms of desensitization for the 5-HT2A and 5-HT2C receptor systems. At very high receptor occupancy (>99%), the responsiveness of the 5-HT2A, but not the 5-HT2C, receptor system returned to control levels despite the continued presence of the agonist. This resensitization was dependent upon the activity of protein kinase C (PKC). Agonist-induced desensitization of the 5-HT2A, but not the 5-HT2C, receptor system was reduced by the PKC inhibitors staurosporine and bisindolylmaleimide, and by down-regulation of PKC. In addition, inhibitors of calmodulin (W-7) or of calmodulin-dependent protein kinase II, reduced 5-HT2A, but not 5-HT2C, desensitization. Desensitization of the 5-HT2C, but not the 5-HT2A, receptor system was dependent on G protein receptor kinase activity. These data further emphasize the major differences in the signaling systems coupled to 5-HT2A/2C receptors." @default.
• W2141175006 created "2016-06-24" @default.
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• W2141175006 date "2001-11-01" @default.
• W2141175006 modified "2023-10-03" @default.
• W2141175006 title "Differences in rapid desensitization of 5-hydroxytryptamine2A and 5-hydroxytryptamine2C receptor-mediated phospholipase C activation." @default.
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• W2141175006 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/11602671" @default.
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