Zhu H, Halaris A, Piletz J E
Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson 39216-4505, USA.
Life Sci. 1997;61(19):1973-83. doi: 10.1016/s0024-3205(97)00837-0.
One subtype of imidazoline receptors (IR1) is similar to alpha 2-adrenoceptors (alpha 2 AR) based on their high affinity for clonidine and related imidazoline compounds. On the other hand, IR1 possess low affinity for norepinephrine (NE) and other catecholamines. Imidazoline receptors have also been found to be over-expressed in plasma membranes from platelets and brain tissues of depressed patients. Over-expression of IR1 in platelet membranes of depressed patients became normalized after various antidepressant treatment to the patients. Herein, the prototypic antidepressant, imipramine (IMI), has been studied in regard to its treatment effects on [125I]p-iodoclonidine binding to both alpha 2 AR and IR1 in rat brainstem membranes. No effects of chronic IMI treatment were found on brainstem alpha 2 AR binding sites (Bmax and/or KD parameters unchanged) after 25 days of daily injections (i.p. IMI 20 mg/kg/day). However, IMI induced a decrease in the density (Bmax measured under NE mask) of brainstem IR1 sites, with no change in KD. Downregulation of IR1 sites was dose-dependent (minimal effective dose of i.p. IMI was 10 mg/kg/day) and time-dependent (> 16 days of treatment). These results implicate brainstem IR1 in the chronic effects of antidepressants.
基于对可乐定及相关咪唑啉化合物的高亲和力，一种亚型的咪唑啉受体（IR1）与α2 - 肾上腺素能受体（α2 AR）相似。另一方面，IR1对去甲肾上腺素（NE）和其他儿茶酚胺的亲和力较低。人们还发现，抑郁症患者血小板和脑组织的质膜中咪唑啉受体过度表达。对抑郁症患者进行各种抗抑郁治疗后，其血小板膜中IR1的过度表达恢复正常。在此，对典型抗抑郁药丙咪嗪（IMI）在大鼠脑干膜中对[125I] - 对碘可乐定与α2 AR和IR1结合的治疗效果进行了研究。每日腹腔注射丙咪嗪20mg/kg/天，持续25天后，未发现慢性丙咪嗪治疗对脑干α2 AR结合位点有影响（Bmax和/或KD参数未改变）。然而，丙咪嗪可导致脑干IR1位点密度降低（在NE掩盖下测量Bmax），而KD无变化。IR1位点的下调呈剂量依赖性（腹腔注射丙咪嗪的最小有效剂量为10mg/kg/天）和时间依赖性（治疗>16天）。这些结果表明脑干IR1与抗抑郁药的慢性作用有关。
