Characterization of mitochondrial imidazoline-guanidinium receptive sites (IGRS) in liver.
Some imidazoline and guanidinium antihypertensive drugs display high affinity for a nonadrenergic membrane protein, the imidazoline-guanidinium receptive site (IGRS), which is insensitive to catecholamine and physically distinct from alpha 2-adrenoceptor. In the present report, we characterized IGRS in human and rabbit liver using [3H]idazoxan as radioligand. By performing subcellular fractionation, we showed a significant increase in [3H]idazoxan binding sites on membrane fractions enriched in cytochrome oxidase activity, a mitochondrial marker. A further enrichment in [3H]idazoxan binding (53-fold with respect to the homogenate) was found in a purified preparation of mitochondrial outer membranes. This localization of IGRS will facilitate the characterization of its functional activity in liver.
Tesson
F
F
Laboratoire de Pharmacologie, Centre National de la Recherche Scientifique, Paris, France.
Prip-Buus
C
C
Lemoine
A
A
Pégorier
J P
JP
Parini
A
A
D000818:Animals; D004146:Dioxanes; D019791:Guanidine; D006146:Guanidines / Q000378:metabolism*; D006801:Humans; D019329:Idazoxan; D054755:Imidazoline Receptors; D007425:Intracellular Membranes / Q000737:chemistry / Q000648:ultrastructure; D008099:Liver / Q000737:chemistry / Q000648:ultrastructure; D008930:Mitochondria, Liver / Q000737:chemistry* / Q000648:ultrastructure*; D011817:Rabbits; D011869:Radioligand Assay; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000378:metabolism; D011955:Receptors, Drug / Q000032:analysis*; D014316:Tritium
D004146:Dioxanes; D006146:Guanidines; D054755:Imidazoline Receptors; D011956:Receptors, Cell Surface; D011955:Receptors, Drug; D014316:Tritium; D019791:Guanidine; D019329:Idazoxan