PT  - JOURNAL ARTICLE
AU  - Frank G. Boess
AU  - Claus Riemer
AU  - Michael Bös
AU  - Jane Bentley
AU  - Anne Bourson
AU  - Andrew J. Sleight
TI  - The 5-Hydroxytryptamine<sub>6</sub> Receptor-Selective radioligand [<sup>3</sup>H]Ro 63–0563 Labels 5-Hydroxytryptamine Receptor Binding Sites in Rat and Porcine Striatum
AID  - 10.1124/mol.54.3.577
DP  - 1998 Sep 01
TA  - Molecular Pharmacology
PG  - 577--583
VI  - 54
IP  - 3
4099  - http://molpharm.aspetjournals.org/content/54/3/577.short
4100  - http://molpharm.aspetjournals.org/content/54/3/577.full
SO  - Mol Pharmacol1998 Sep 01; 54
AB  - Ro 63–0563 [4-amino-N-(2,6 bis-methylamino-pyridin-4-yl)-benzene sulfonamide] is a high affinity 5-hydroxytryptamine6 (HT6) receptor antagonist with more than 100-fold selectivity for the 5-HT6 receptor compared with 69 other receptors and binding sites. The present study describes the properties of [3H]Ro 63–0563, the first selective 5-HT6 receptor radioligand. Specific binding of [3H]Ro 63–0563 (nonspecific binding defined in the presence of 10 μm methiothepin) to recombinant rat and human 5-HT6 receptors was saturable, rapid, and reversible with equilibrium dissociation constants (K d) of 6.8 nmand 4.96 nm, respectively. The pharmacological profile of the rat 5-HT6 receptor labeled with [3H]Ro 63–0563 (methiothepin > d-lysergic acid diethylamide > clozapine ∼ Ro 63–0563 > lisuride > ergotamine ∼ Ro 04–6790 > 5-HT > amitriptyline ∼ metergoline ∼ mianserin ∼ ritanserin > methysergide > mesulergine) was similar to that obtained by using either [3H]d-lysergic acide diethylamide or [3H]5-HT as radioligand. In equilibrium binding studies with rat striatal membranes, [3H]Ro 63–0563 labeled a single binding site with K d andB max values of 11.7 nm and 175 fmol/mg protein, respectively. In porcine striatal membranes, [3H]Ro 63–0563 also labeled a single binding site withK d andB max values of 8.0 nm and 130 fmol/mg protein, respectively. The affinities of 14 5-HT6 receptor ligands at this binding site were similar to those found for the recombinant rat and human 5-HT6receptor, which suggested the presence of 5-HT6 receptors in porcine striatum.