大鼠慢性全身给药沙美特罗可促进肺β(2)肾上腺素受体脱敏和G(s α)下调。
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芬尼PA，唐纳利LE，贝尔维西MG，庄TT，伯雷尔M，哈里斯A，麦JC，得分手C，巴恩斯PJ，阿德考克IM，吉姆拜茨MA
大鼠慢性全身给药沙美特罗可促进肺β(2)肾上腺素受体脱敏和G(s α)下调。
中国药物学杂志，2001 3月;132(6):1261-70。
- PubMed ID
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11250877 (PubMed视图］
- 摘要
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1.本研究的目的是检查长期输注长效激动剂沙美特罗对Sprague-Dawley大鼠体内肺β(2)肾上腺素能受体功能的影响，并阐明任何改变状态的分子基础。2.大鼠全身给药沙美特罗7天，与同样给药的大鼠相比，沙美特罗和前列腺素E(2) (PGE(2))通过静脉急性给药对ach诱导的支气管收缩的保护能力下降。3.沙美特罗处理过的动物肺膜中β(1)-和β(2)-肾上腺素能受体密度显著降低，这与沙美特罗和PGE(2)诱导的体外循环AMP积累受损有关。4.在两组大鼠制备的肺膜中都检测到G(s α)的三种变体，它们以42、44和52 kDa多肽的形式在SDS聚丙烯酰胺凝胶上迁移，但每种亚型的强度在接受沙美特罗的大鼠中显著降低。5.与载体处理的动物相比，沙美特罗处理的大鼠肺中g蛋白受体偶联激酶的细胞质(而非膜相关)活性升高。 6. The ability of salmeterol, administered systemically, to protect the airways of untreated rats against ACh-induced bronchoconstriction was short-acting (t(off) approximately 45 min), which contrasts with its long-acting nature when given to asthmatic subjects by inhalation. 7. These results indicate that chronic treatment of rats with salmeterol results in heterologous desensitization of pulmonary G(s)-coupled receptors. In light of previous data obtained in rats treated chronically with salbutamol, we propose that a primary mechanism responsible for this effect is a reduction in membrane-associated G(s alpha). The short-acting nature of salmeterol, when administered systemically, and the reduction in beta-adrenoceptor number may be due to metabolism to a biologically-active, short-acting and non-selective beta-adrenoceptor agonist.