Autoradiographic mapping of 5-HT1B- and 5-HT1D receptors in human brain using [3H]alniditan, a new radioligand.
[3H]alniditan, a new potent non-indole serotonin 5-HT1B/1D agonist, was used as a radioligand to characterize 5-HT1B and 5-HT1D receptor (previously termed 5-HT1D beta and 5-HT1D alpha) in various regions of the human brain. Quantitative receptor autoradiography was applied for high anatomical resolution and sensitivity. Highest densities of 5-HT1B/1D receptors were found in the substantia nigra and in the globus pallidus. High to moderate densities were measured in the caudate nucleus, putamen, nucleus accumbens, central gray and hippocampal formation. Very low densities were detected in various cortical regions. In the cerebellum no [3H]alniditan binding was detected. Selective 5-HT1B receptor labeling was achieved using [3H]alniditan in the presence of 300 nM of ketanserin (sufficient to block 5-HT1D receptor labeling). The identity of the 5-HT1B binding sites under these conditions was corroborated by the pIC50 of sumatriptan, which corresponded to its affinity for cloned human 5-HT1B receptors expressed in cells. Surprisingly, the distribution of selective 5-HT1B receptor labeling was completely identical to the distribution of labeling of 5-HT1B + 5-HT1D receptors. The present data indicate that [3H]alniditan is a suitable radioligand for measuring 5-HT1B/1D receptor in the human brain and that the 5-HT1B binding sites are predominant in the presently investigated regions of the human brain.
Bonaventure
P
P
Department of Biochemical Pharmacology, Janssen Research Foundation, Beerse, Belgium. pbonaven@janbe.jnj.com
Schotte
A
A
Cras
P
P
Leysen
J E
JE
D000818:Animals; D001578:Benzopyrans / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D007553:Isotope Labeling; D008024:Ligands; D008297:Male; D008875:Middle Aged; D011437:Propylamines / Q000378:metabolism*; D011743:Pyrimidines / Q000378:metabolism*; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin / Q000378:metabolism*; D014316:Tritium
D001578:Benzopyrans; C470302:HTR1B protein, human; D008024:Ligands; D011437:Propylamines; D011743:Pyrimidines; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin; D014316:Tritium; C100822:alniditan