IDENTIFICATION OF 5-HYDROXYTRYPTAMINE(10) BINDING-SITES IN SHEEP CAUDATE-NUCLEUS MEMBRANES

Radioligand binding measurements were performed in membranes of sheep caudate nucleus using [H-3]5-hydroxytryptamine (5-HT). [H-3]5-HT labeled a population of high affinity binding sites with a K(d) of 1.9 +/- 0.1 nM and a B(max) of 19.8 +/- 2.2 fmol/mg tissue. Combined 5-HT1D/E binding sites were the predominant 5-HT, 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.