Leysen J E, Gommeren W, Janssen P A
Department of Biochemical Pharmacology, Janssen Research Foundation, Beerse, Belgium.
Eur J Pharmacol. 1991 Jan 25;206(1):39-45. doi: 10.1016/0922-4106(91)90144-7.
[3H]Ketanserin was found to label (besides a low amount of 5-HT2 receptors) non-serotonergic binding sites on human platelet membranes. The latter binding was detected in the presence of excess of the 5-HT2 antagonist BW501, and was potently inhibited by tetrabenazine. [3H]Ketanserin revealed a KD value = 19 +/- 4 nM and a Bmax = 425 +/- 82 fmol/10(9) platelets for these binding sites. [3H]Ketanserin binding in the presence of BW501 was inhibited by the tetrabenazine derivative RO-4-1284 (IC50 = 1.4 nM), tetrabenazine (IC50 = 8.6 nM) and the ketanserin derivatives R 71,278 (IC50 = 6.3 nM), R 47,288 (IC50 = 17 nM) and R 71,428 (IC50 = 100 nM). Ketanserin revealed an IC50 = 32 nM. The drugs were found to trigger the release of 3H from [3H]5-HT-loaded human platelets in superfusion experiments in vitro. The amount of 3H released by the drugs correlated with their binding affinities for the non-serotonergic sites. The non-serotonergic [3H]ketanserin binding sites on human platelets and their possible role in triggering monoamine release corresponded to the properties of non-serotonergic ketanserin binding sites previously characterized in rat striatum. The possible role of the action of ketanserin on the non-serotonergic sites in the reported partial reduction by ketanserin of the monoamine content in cardiovascular tissues is discussed.
已发现[3H]酮色林除标记少量5-HT2受体外，还能标记人血小板膜上的非5-羟色胺能结合位点。后者的结合在存在过量5-HT2拮抗剂BW501的情况下被检测到，并且被丁苯那嗪强烈抑制。对于这些结合位点，[3H]酮色林显示出KD值=19±4 nM，Bmax=425±82 fmol/10(9)个血小板。在BW501存在下的[3H]酮色林结合被丁苯那嗪衍生物RO-4-1284（IC50=1.4 nM）、丁苯那嗪（IC50=8.6 nM）以及酮色林衍生物R 71,278（IC50=6.3 nM）、R 47,288（IC50=17 nM）和R 71,428（IC50=100 nM）抑制。酮色林显示出IC50=32 nM。在体外灌注实验中，发现这些药物能触发[3H]5-羟色胺负载的人血小板释放3H。药物释放的3H量与其对非5-羟色胺能位点的结合亲和力相关。人血小板上的非5-羟色胺能[3H]酮色林结合位点及其在触发单胺释放中的可能作用与先前在大鼠纹状体中表征的非5-羟色胺能酮色林结合位点的特性相符。讨论了酮色林作用于非5-羟色胺能位点在报告的酮色林使心血管组织中单胺含量部分降低中的可能作用。
