5-HT1D binding sites in porcine brain can be sub-divided by GR43175.
We have examined the binding of 5-carboxamidotryptamine (5-CT) and GR43175 (3-(2-dimethylamino)ethyl-N-methyl-1H-indole-5-methane sulphonamide) to 5-HT1D sites labelled with [3H]-5-hydroxytryptamine [( 3H]-5-HT) in neonatal porcine caudate membranes. In competition studies, 5-CT produced shallow inhibition curves (Ki 138 nM, slope 0.31), indicating binding site heterogeneity, while GR43175 interacted with a single population of binding sites (Ki 251 nM, slope 0.98), producing a maximum of only 52% inhibition of [3H]-5-HT binding compared to 100% for 5-HT or 5-CT. In the presence of excess GR43175 (10 microM), 5-CT produced a monophasic inhibition curve with a Ki value of 800 nM for the remaining sites (slope 0.89). These preliminary data suggest that under the conditions employed, GR43175, and to a lesser extent 5-CT, may discriminate between two sub-populations of 5-HT1D binding sites in porcine brain.
Sumner
M J
MJ
Pharmacology Division, Glaxo Group Research, Hertfordshire.
Humphrey
P P
PP
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002421:Caudate Nucleus / Q000378:metabolism; D066298:In Vitro Techniques; D007211:Indoles; D007700:Kinetics; D008297:Male; D011985:Receptors, Serotonin / Q000378:metabolism*; D013449:Sulfonamides; D018170:Sumatriptan; D013552:Swine
D007211:Indoles; D011985:Receptors, Serotonin; D013449:Sulfonamides; D018170:Sumatriptan