کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2201696 | 1100035 | 2007 | 10 صفحه PDF | دانلود رایگان |
The present study aimed at elucidating the molecular identity of the proposed “I1-imidazoline receptors”, i.e. non-adrenoceptor recognition sites via which the centrally acting imidazolines clonidine and moxonidine mediate a major part of their effects. In radioligand binding experiments with [3H]clonidine and [3H]lysophosphatidic acid on intact, α2-adrenoceptor-deficient PC12 cells, moxonidine, clonidine, lysophosphatidic acid and sphingosine-1-phosphate (S1P) competed for the specific binding sites of both radioligands with similar affinities. RNA interference with the rat S1P1-, S1P2- or S1P3-receptor abolished specific [3H]lysophosphatidic acid binding. [3H]Clonidine binding was markedly decreased by siRNA targeting S1P1- and S1P3-receptors but not by siRNA against S1P2-receptors. Finally, in HEK293 cells transiently expressing human S1P3-receptors, sphingosine-1-phosphate, clonidine and moxonidine induced increases in intracellular calcium concentration, moxonidine being more potent than clonidine; this is in agreement with the known properties of the “I1-imidazoline receptors”.The present results indicate that the “I1-imidazoline receptors” mediating effects of clonidine and moxonidine in PC12 and the transfected HEK293 cells belong to the S1P-receptor family; in particular, the data obtained in PC12 cells suggest that the I1 imidazoline receptors represent a mixture of S1P1- and S1P3-receptors and/or hetero-dimers of both.
Journal: Neurochemistry International - Volume 51, Issue 8, December 2007, Pages 476–485