Characterization of [3H]CP-96,501 as a selective radioligand for the serotonin 5-HT1B receptor: binding studies in rat brain membranes.
3-(1,2,5,6-Tetrahydro-4-pyridyl)-5-n-propoxyindole (CP-96,501) was found to be more selective ligand at the serotonin 5-HT1B receptor than the commonly used 5-HT1B agonist, 3-(1,2,5,6-tetrahydro-4-pyridyl)-5-methoxyindole (RU 24969). In rat brain membranes, the tritiated derivative, [3H]CP-96,501, was found to bind with a high affinity (KD, 0.21 nM) to a single binding site (nH, 1.0). The receptor density of this site (Bmax, 72 fmol/mg of protein) matched that of the 5-HT1B receptor determined with [3H]5-HT. Competition curves of 16 serotonergic compounds in [3H]CP-96,501 binding also indicated a single binding site. The rank order of their binding affinities with this new radioligand showed a high degree of correlation with their affinities at the 5-HT1B receptor determined with [3H]5-HT or [125I]iodocyanopindolol. Serotonergic compounds displayed competitive inhibition of [3H]CP-96,501 binding. In the presence of 5'-guanylylimidodiphosphate [Gpp(NH)p], [3H]CP-96,501 to displace [125I]iodocyanopindolol binding was also decreased. These findings are consistent with the agonist nature of CP-96,501. The results of this study suggest that [3H]CP-96,501 is a useful agonist radioligand for the 5-HT1B receptor.
Koe
B K
BK
Department of Neuroscience, Pfizer Inc., Groton, Connecticut 06340.
Lebel
L A
LA
Fox
C B
CB
Macor
J E
JE
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D006150:Guanine Nucleotides / Q000494:pharmacology; D007211:Indoles / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D008024:Ligands; D051381:Rats; D011985:Receptors, Serotonin / Q000378:metabolism*; D014316:Tritium
D006150:Guanine Nucleotides; D007211:Indoles; D008024:Ligands; D011985:Receptors, Serotonin; D014316:Tritium; C073516:3-(1,2,5,6-tetrahydro-4-pyridyl)-5-n-propoxyindole