Paradoxical trafficking and regulation of 5HT2A receptors by agonists and antagonists

被引:237
作者
Gray, JA
Roth, BL
机构
[1] Case Western Reserve Univ, Sch Med, Dept Biochem, Cleveland, OH 44106 USA
[2] Case Western Reserve Univ, Sch Med, Dept Psychiat, Cleveland, OH 44106 USA
[3] Case Western Reserve Univ, Sch Med, Dept Neurosci, Cleveland, OH 44106 USA
关键词
down-regulation; antipsychotic; antidepressant; internalization; clozapine; arrestin;
D O I
10.1016/S0361-9230(01)00623-2
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
5-Hydroxytryptamine(2A) (serotonin(2A), 5-HT2A) receptors are Important for many physiologic processes including platelet aggregation, smooth muscle contraction, and the modulation of mood and perception. A large number of pharmaceutical agents mediate their actions, at least in part, by modulating the number and/or activity of 5-HT2A receptors. Drugs with action at 5-HT2A receptors are used in the treatment of many disorders, including schizophrenia, depression, and anxiety disorders. This review summarizes over two decades of research on the regulation of 5-HT2A receptors and provides a comprehensive review of numerous in vivo studies describing the paradoxical phenomenon of 5-HT2A receptor down-regulation by chronic treatment with antidepressants and antipsychotics. In addition, studies reporting antagonist-induced internalization of 5-HT2A receptors and other G protein-coupled receptors will be highlighted as a possible mechanism to explain this paradoxical down-regulation. Finally, a review of the cellular and molecular mechanisms that may be responsible for agonist-mediated desensitization and internalization of 5-HT2A receptors will be presented. (C) 2001 Elsevier Science Inc.
引用
收藏
页码:441 / 451
页数:11
相关论文
共 109 条
[1]  
AKIYOSHI J, 1993, MOL PHARMACOL, V43, P349
[2]   DIFFERENTIAL EFFECT OF SUBCHRONIC TREATMENT WITH VARIOUS NEUROLEPTIC AGENTS ON SEROTONIN2 RECEPTORS IN RAT CEREBRAL-CORTEX [J].
ANDREE, TH ;
MIKUNI, M ;
TONG, CY ;
KOENIG, JI ;
MELTZER, HY .
JOURNAL OF NEUROCHEMISTRY, 1986, 46 (01) :191-197
[3]   Effects of selective serotonin reuptake inhibitors on platelet serotonin parameters in major depressive disorder [J].
Bakish, D ;
Cavazzoni, P ;
Chudzik, J ;
Ravindran, A ;
Hrdina, PD .
BIOLOGICAL PSYCHIATRY, 1997, 41 (02) :184-190
[4]  
BERGSTROM DA, 1979, J PHARMACOL EXP THER, V209, P256
[5]  
Berry SA, 1996, MOL PHARMACOL, V50, P306
[6]   The dynamin-dependent, arrestin-independent internalization of 5-hydroxytryptamine 2A (5-HT2A) serotonin receptors reveals differential sorting of arrestins and 5-HT2A receptors during endocytosis [J].
Bhatnagar, A ;
Willins, DL ;
Gray, JA ;
Woods, J ;
Benovic, JL ;
Roth, BL .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (11) :8269-8277
[7]   ACUTE AND CHRONIC EFFECTS OF SEROTONIN (5HT) ANTAGONISTS ON SEROTONIN BINDING-SITES [J].
BLACKSHEAR, MA ;
FRIEDMAN, RL ;
SANDERSBUSH, E .
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 1983, 324 (02) :125-129
[8]  
BLACKSHEAR MA, 1982, J PHARMACOL EXP THER, V221, P303
[9]   SEROTONIN2 AGONIST ADMINISTRATION DOWN-REGULATES RAT-BRAIN SEROTONIN2 RECEPTORS [J].
BUCKHOLTZ, NS ;
ZHOU, DF ;
FREEDMAN, DX .
LIFE SCIENCES, 1988, 42 (24) :2439-2445
[10]   DAILY LSD ADMINISTRATION SELECTIVELY DECREASES SEROTONIN2 RECEPTOR-BINDING IN RAT-BRAIN [J].
BUCKHOLTZ, NS ;
FREEDMAN, DX ;
MIDDAUGH, LD .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1985, 109 (03) :421-425