Matthews E K, Mesler D E
Br J Pharmacol. 1984 Oct;83(2):555-66. doi: 10.1111/j.1476-5381.1984.tb16520.x.
Photon activation of the halogenated fluorescein derivative erythrosine caused a marked calcium-dependent contraction of the smooth muscle cells of the guinea-pig taenia coli superfused in vitro. Neither high intensity illumination alone (up to 5 X 10(4) lux) nor erythrosine alone (up to 2 X 10(-4) M) altered the tone of the taenia or its ability to respond to carbachol (5 X 10(-5) M); photo-irradiation of erythrosine before tissue contact was also ineffective. The magnitude of the photodynamic contraction was dependent upon the concentration of erythrosine, the intensity and wavelength of the incident light, and the presence of oxygen; indirect effects via neurotransmitter release or cyclo-oxygenase activation were specifically excluded. The photodynamic response was blocked by zero-[Ca]o and addition of EGTA (1 mM) but not by omission of [Mg]o or a decrease in [Cl]o or [Na]o. D600 (methoxyverapamil) 10(-5) M, or a ten fold increase in [Mg]o, to 11.3 mM, partly inhibited the photodynamic contraction at low, but not high, light intensities. These observations are consistent with the following sequence of events: (i) photo-activation of the erythrosine molecule, (ii) the generation of highly reactive singlet oxygen, (iii) local peroxidation of cell membrane proteolipid, (iv) increased membrane permeability to Ca2+, (v) the influx of Ca2+ and, (vi) muscle contraction. It is concluded that the photodynamic action of erythrosine presents a novel method for modulation of membrane calcium permeability, and hence [Ca]i, not only in smooth muscle but possibly in other cells as well, e.g., secretory, epithelial and myocardial cells.
卤化荧光素衍生物赤藓红的光子激活导致体外灌流的豚鼠结肠带平滑肌细胞出现明显的钙依赖性收缩。单独的高强度光照(高达5×10⁴勒克斯)或单独的赤藓红(高达2×10⁻⁴M)均未改变结肠带的张力或其对卡巴胆碱(5×10⁻⁵M)的反应能力;在组织接触前对赤藓红进行光照射也无效。光动力收缩的幅度取决于赤藓红的浓度、入射光的强度和波长以及氧气的存在;特别排除了通过神经递质释放或环氧化酶激活产生的间接影响。光动力反应被零钙外液和添加EGTA(1 mM)阻断,但不被去除镁外液或降低氯外液或钠外液阻断。10⁻⁵M的D600(甲氧基维拉帕米)或将镁外液浓度提高10倍至11.3 mM,在低光照强度下部分抑制光动力收缩,但在高光照强度下则不然。这些观察结果与以下事件序列一致:(i)赤藓红分子的光激活,(ii)高活性单线态氧的产生,(iii)细胞膜蛋白脂质的局部过氧化,(iv)细胞膜对Ca²⁺通透性增加,(v)Ca²⁺内流,以及(vi)肌肉收缩。得出的结论是,赤藓红的光动力作用不仅为调节平滑肌,而且可能为调节其他细胞(如分泌细胞、上皮细胞和心肌细胞)的膜钙通透性以及因此的细胞内钙浓度提供了一种新方法。