Quantitative autoradiography of 5-CT-sensitive (5-HT1D) and 5-CT-insensitive (5-HT1E) serotonin receptors in human brain.
Quantitative receptor autoradiography was used to determine the distribution patterns of 5-CT-sensitive and 5-CT-insensitive binding of [3H]5-HT to high-affinity sites in human cortex, putamen, and globus pallidus. The binding of 3H-5-HT was limited to 5-HT1D sites (5-CT-sensitive) by co-incubating pindolol and mesulergine with [3H]5-HT, and by using 10 microM 5-HT to determine non-specific binding. The difference in the levels of binding between tissues exposed to the 5-CT-containing incubation media and tissue exposed to [3H]5-HT in the presence of 100 nM 5-CT was defined as 5-CT-insensitive binding (5-HT1E). The 5-HT1D receptor density in the frontal cortex was 189 fmol/mg, 226 fmol/mg was present in the globus pallidus, while the density in the putamen was only 28 fmol/mg. The 5-HT1E receptor density was 146 fmol/mg in frontal cortex, 224 fmol/mg in putamen and 140 fmol/mg in globus pallidus. The differential distribution patterns of the high-affinity, 5-CT-sensitive and 5-CT-insensitive [3H]5-HT binding sites indicate that these sites are expressed independently in human brain tissues. These data are supportive of and consistent with previous pharmacological data that led to the division of 5-HT1D receptors into 5-HT1D and 5-HT1E receptors and do not support the division of 5-HT1D receptors into 5-CT-sensitive and 5-CT-insensitive states.
Miller
K J
KJ
Department of Pharmacology and Toxicology, Albany Medical College, NY 12208.
Teitler
M
M
D000978:Antiparkinson Agents / Q000494:pharmacology; D001345:Autoradiography; D001923:Brain Chemistry / Q000187:drug effects*; D004873:Ergolines / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D010869:Pindolol / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000031:analogs & derivatives* / Q000494:pharmacology
D000978:Antiparkinson Agents; D004873:Ergolines; D011985:Receptors, Serotonin; D012701:Serotonin; C047087:5-carboxamidotryptamine; D010869:Pindolol; C031649:mesulergine