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Drummond AH, Gordon JL.
“Inhibition of 5-Hydroxy-(3H)-tryptamine Binding to Rat Blood Platelets by 5-HT Antagonists and Uptake Inhibitors”.
Brit.J.Pharmacol.. 1975;55(2):257P-58P.
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Abstract
The relationships between 5HT binding of the two highest (of 3) affinity rat platelet 5-HT binding sites, production of the 5-HT induced shape change and the active uptake of 5-HT were studied in rat citrated platelet-rich plasma. Specific binding of (3H)-5-HT was essentially instantaneous and was directly proportional to the number of platelets. Binding to the highest affinity site (Ka -1 = 10 nM) was prevented by 5-HT antagonists such as methergoline (IC50 = 0.7 nM). There was good correlation between inhibition of this (3H)-5-HT binding and inhibition of the 5-HT-induced shape change with compounds including pizatifen, D-LSD, cyproheptadine, cinanserin, methysergide, xylamidine, chlorpromazine, imipramine, chlorimipramine, Lilly 110140 and Lilly 103947 (3-(p-trifluoromethylphenoxy) 3-phenylpropylamine). Inhibitors of 5-HT uptake also affected shape change and binding to the highest affinity site. Binding of (3H)-5-HT to the middle affinity site (Ka-1 = 0.1 M) was insensitive to 5-HT antagonists, but blocked by 5-HT uptake inhibitors. There was good correlation between inhibition of 5-HT uptake and inhibition of binding to the middle affinity site for chlorimipramine (IC50 value against uptake, 0.2 mcM), Lilly 103947 (0.25 mcM), Lilly 110140 (O.5 mcM), imipramine (0.7 mcM), amitriptyline (1.2 mcM) and desmethylimipramine (7.5 mcM). The results suggest that the binding of (3H)-5-HT to the highest affinity site is involved in the production of the platelet shape change and that the middle affinity site may be related to the c:arrier for the active transport of 5-HT.
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