Identification of 5-hydroxytryptamine1D binding sites in sheep caudate nucleus membranes.
Radioligand binding measurements were performed in membranes of sheep caudate nucleus using [3H]5-hydroxytryptamine (5-HT). [3H]5-HT labeled a population of high affinity binding sites with a Kd of 1.9 +/- 0.1 nM and a Bmax of 19.8 +/- 2.2 fmol/mg tissue. Combined 5-HTID/E binding sites were the predominant 5-HT1 subtype, accounting for 78% of the total population of 5-HT1 binding sites. 5-Carboxamidotryptamine (5-CT) and sumatriptan yielded inhibition curves which best fitted a two-site model with high affinity values of 0.8 and 10.1 nM, and 1000 and 206 nM for their low affinity components. The proportion of the high affinity 5-CT and sumatriptan binding sites was 79 and 72%. The binding affinity profile of 5-HT1D binding sites [5-CT > 5-HT > d-LSD > 5-MeOT > sumatriptan > RU 24,969 > metergoline > tryptamine = rauwolscine = methylsergide > yohimbine = methiothepin > TFMPP = 8-OH-DPAT > 2-methyl-5-HT > mCPP = quipazine = CP 93,129 > ketanserin > (-)-propranolol = haloperidol = ipsapirone] compares well to that reported for 5-HT1D receptor sites in human caudate and cortex (correlation coefficient: 0.99 and 0.98). The present results indicate that sheep caudate nucleus is a valid tissue for studying interaction of compounds with 5-HT1D binding sites in the relative absence of 5-HT1E binding sites.
Laboratory of Cellular Neurobiology, Centre de Recherche Pierre Fabre, Castres, France.
P J
PJ
Pauwels
C
C
Palmier
M
M
Briley
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D002421:Caudate Nucleus / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D004873:Ergolines / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000378:metabolism* / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D012756:Sheep; D013449:Sulfonamides / Q000494:pharmacology; D018170:Sumatriptan; D014316:Tritium
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D004873:Ergolines; D007211:Indoles; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D013449:Sulfonamides; D018170:Sumatriptan; D014316:Tritium; C031649:mesulergine