Pharmacological modulation of immunoreactive imidazoline receptor proteins in rat brain: Relationship with non-adrenoceptor [H-3]-idazoxan binding sites
Pharmacological modulation of immunoreactive imidazoline receptor proteins in rat brain: Relationship with non-adrenoceptor [H-3]-idazoxan binding sites
复制标题
DOI：
10.1111/j.1476-5381.1996.tb15640.x
复制
发表时间：
1996-08-01
影响因子：
7.3
通讯作者：
GarciaSevilla, JA
中科院分区：
文献类型：
--
作者：
Escriba, PV;Alemany, R;GarciaSevilla, JA
1用免疫印迹法检测不同药物处理后大鼠大脑皮质中各种咪唑啉受体蛋白(表观分子质量约为29/30~45-和66-kDa)的密度。然后比较这些咪唑啉受体蛋白的调节与相同药物治疗引起的非肾上腺素受体[H-3]-咪唑恶生结合位点(I-2-位点)密度的变化。2慢性治疗(7天)，I-2选择性咪唑(I-2)选择性药物咪唑克生(10 mg kg(-1))、齐拉唑啉(1 mg kg(-1))和LSL 60101(10 mg kg(-1))可不同程度地增强咪唑啉受体蛋白的免疫反应活性。咪唑克生和LSL 60101使29/30 kDa蛋白表达增加(23%)，45 kDa蛋白表达增加(44%)，66 kDa蛋白表达增加(50%)。这些药物治疗还增加了I-2-位点的密度(32-42%)。3慢性治疗(7天)：依福生(10 mg kg(-1))，RX821002(10 mg kg(-1))和育亨宾(10 mg kg(-1))，它们对I-2-咪唑啉受体的亲和力很低，4用单胺氧化酶(MAO)抑制剂Clorgyline(10 mg kg(-1))和苯乙肼(10 mg kg(-1))慢性处理(7天)后，29/30 kDa(17-24%)、45-kDa(19%)和66-kDa(23-31%)咪唑啉受体蛋白的免疫反应性降低。烷化剂N-ethoxycarbonyl-2-ethoxy-1，2-dihydroquinoline(1.6 mg·kg~(-1))作用6h后，3种咪唑啉受体蛋白的表达水平也降低了20~47%。这些药物治疗持续降低I-2-位点密度(31-57%)。5当咪唑啉受体蛋白免疫反应性的平均百分比变化与不同药物治疗后I-2-位点密度的平均百分比变化相关时，发现显著的相关性(对于29/30 kDa蛋白，r=0.92，6在大鼠大脑皮层，[H-3]-咪唑啉标记的I-2-咪唑啉受体是异质性的，免疫印迹检测到相关的咪唑啉受体蛋白(29/30-、45-和66-kDa)对药物治疗后I-2-位点的调控有不同的作用。
1 The densities of various imidazoline receptor proteins (with apparent molecular masses of approximate to 29/30- 45- and 66-kDa) were quantitated by immunoblotting in the rat cerebral cortex after various drug treatments. The modulation of these imidazoline receptor proteins was then compared with the changes in the density of non-adrenoceptor [H-3]-idazoxan binding sites (I-2-sites) induced by the same drug treatments.2 Chronic treatment (7 days) with the I-2-selective imidazol(in)e drugs idazoxan (10 mg kg(-1)), cirazoline (1 mg kg(-1)) and LSL 60101 (10 mg kg(-1)) differentially increased the immunoreactivity of imidazoline receptor proteins. The levels of the 29/30-kDa protein were increased by idazoxan and LSL 60101 (23%), the levels of the 45-kDa protein only by cirazoline (44%) and those of the 66-kDa protein only by idazoxan (50%). These drug treatments also increased the density of I-2-sites (32-42%).3 Chronic treatment (7 days) with efaroxan (10 mg kg(-1)), RX821002 (10 mg kg(-1)) and yohimbine (10 mg kg(-1)), which possess very low affinity for I-2-imidazoline receptors, did not alter either the immunoreactivity of imidazoline receptor proteins or the density of I-2-sites.4 Chronic treatment (7 days) with the monoamine oxidase (MAO) inhibitors clorgyline (10 mg kg(-1)) and phenelzine (10 mg kg(-1)) decreased the immunoreactivity of the 29/30-kDa (17-24%), 45-kDa (19%) and 66-kDa (23-31%) imidazoline receptor proteins. The alkylating agent N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (1.6 mg kg(-1) 6 h) also decreased the levels of the three imidazoline receptor proteins (20-47%). These drug treatments consistently decreased the density of I-2-sites (31-57%).5 Significant correlations were found when the mean percentage changes in immunoreactivity of imidazoline receptor proteins were related to the mean percentage changes in the density of I-2-sites after the various drug treatments (r = 0.92 for the 29/30-kDa protein, r = 0.69 for the 45-kDa protein and r = 0.75 for the 66-kDa protein).6 In the rat cerebral cortex the I-2-imidazoline receptor labelled by [H-3]-idazoxan is heterogeneous in nature and the related imidazoline receptor proteins (29/30-, 45- and 66-kDa) detected by immunoblotting contribute differentially to the modulation of I-2-sites after drug treatment.