Selective visualization of rat brain 5-HT2A receptors by autoradiography with [3H]MDL 100,907.
The recently developed 5-HT2A receptor selective antagonist [3H]MDL100,907 ((+/-)2,3-dimethoxyphenyl-1-[2-(4-piperidine)-methanol]) has been characterized as a radioligand for the autoradiographic visualization of these receptors. [3H]MDL100,907 binding to rat brain tissue sections was saturable, had sub-nanomolar affinity (Kd = 0.2-0.3 nM), and presented a pharmacological profile consistent with its binding to 5-HT2A receptors (rank order of affinity for [3H]MDL100,907-labelled receptors: MDL100,907 > spiperone > ketanserin > mesulergine). The distribution of receptors labelled by [3H]MDL100,907 was compared to the autoradiographical patterns obtained with [3H]Ketanserin, [3H]Mesulergine, and [3H]RP62203 (N-[3-[4-(4-fluorophenyl)piperazin-1-y1]propyl]-1,8-naphtalenes ultam) and to the distribution of 5-HT2A receptor mRNA as determined by in situ hybridization. As opposed to the other radioligands, [3H]MDL100,907 labelled a single population of sites (5-HT2A receptors) and presented extremely low levels of non-specific binding. The close similarity of the distributions of [3H]MDL100,907-labelled receptors and 5-HT2A mRNA further supports the selectivity of this radioligand for 5-HT2A receptors and suggests a predominant somatodendritic localization of these receptors. The present results point to [3H]MDL100,907 as the ligand of choice for the autoradiographic visualization of 5-HT2A receptors.
López-Giménez
J F
JF
Department of Neurochemistry, Instituto de Investigaciones Biomédicas de Barcelona, Consejo Superior de Investigaciones Científicas (CSIC), Spain.
Mengod
G
G
Palacios
J M
JM
Vilaró
M T
MT
D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D003499:Cyclic S-Oxides / Q000378:metabolism; D004873:Ergolines / Q000378:metabolism; D005464:Fluorobenzenes / Q000378:metabolism; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D007650:Ketanserin / Q000378:metabolism; D008297:Male; D009281:Naphthalenes / Q000378:metabolism; D010880:Piperidines / Q000378:metabolism; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000378:metabolism
D003499:Cyclic S-Oxides; D004873:Ergolines; D005464:Fluorobenzenes; D009281:Naphthalenes; D010880:Piperidines; D012333:RNA, Messenger; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D006165:Guanylyl Imidodiphosphate; C070475:fananserin; D007650:Ketanserin; C079049:volinanserin; C031649:mesulergine