Aboulafia J, Oshiro M E, Feres T, Shimuta S I, Paiva A C
Escola Paulista de Medicina, Department of Biophysics, São Paulo, Brazil.
Pflugers Arch. 1989 Nov;415(2):230-4. doi: 10.1007/BF00370597.
The role of ion fluxes in angiotensin II (AII) desensitization (tachyphylaxis) was investigated by studying Na+ and Ca2+ translocation in cultured vascular smooth muscle cells from the rat aorta. The effects of AII were compared to those of [1-sarcosine]-AII (Sar1-AII), an analogue which also induces tachyphylaxis, and [2-lysine]-AII (Lys2-AII), an analogue that does not show this property. Maximally effective concentrations of the three peptides induced a rapid and transient increase in 45Ca2+ efflux, a rapid and sustained decrease in total cell Ca2+ and an increased Na+ permeability. Repeated treatments, at short intervals, with either of the three peptides abolished the effect on Ca2+ efflux, and this desensitization was slowly reversible. A 30-min rest period was sufficient for full recovery of the response of cells that were desensitized by Lys2-AII, whereas the recovery from AII or Sar1-AII-desensitization was still not complete after 60 min. Our results suggest that the difference in the behaviour of the "tachyphylactic" AII and Sar1-AII and the "non-tachyphylactic" Lys2-AII lays not in the production of different signals upon binding to the receptor, but in a difference in the hormone-receptor interaction itself.
通过研究大鼠主动脉培养的血管平滑肌细胞中Na+和Ca2+的转运，探讨了离子通量在血管紧张素II（AII）脱敏（快速耐受性）中的作用。将AII的作用与[1-肌氨酸]-AII（Sar1-AII，一种也能诱导快速耐受性的类似物）和[2-赖氨酸]-AII（Lys2-AII，一种不具有此特性的类似物）的作用进行了比较。三种肽的最大有效浓度均诱导45Ca2+外流迅速短暂增加、细胞总Ca2+迅速持续减少以及Na+通透性增加。短时间间隔内用三种肽中的任何一种重复处理均可消除对Ca2+外流的影响，且这种脱敏作用是缓慢可逆的。30分钟的休息期足以使被Lys2-AII脱敏的细胞反应完全恢复，而60分钟后，AII或Sar1-AII脱敏后的恢复仍不完全。我们的结果表明，“快速耐受性”AII和Sar1-AII与“非快速耐受性”Lys2-AII行为的差异不在于与受体结合时产生不同信号，而在于激素-受体相互作用本身的差异。
