Developmental aspects of bladder contractile function: sensitivity to extracellular calcium.
Developmental aspects of bladder contractile function: sensitivity to extracellular calcium.
复制标题
膀胱收缩功能的发育方面：对细胞外钙的敏感性。
作者：
Zderic,SA;Hypolite,J;Duckett,JW;Snyder3rd,HM;Wein,AJ;Levin,RM
1日龄和1周龄家兔的膀胱在比乙二酚和电场刺激下产生的膀胱压力高于8周龄家兔的膀胱。然而，兔膀胱胆碱能受体的密度不随成熟（1天至8周）而变化。为了更好地理解新生兔膀胱比成年兔膀胱产生更大压力的分子机制，我们研究了成熟对细胞外钙和收缩之间关系的影响。我们的结果非常清楚地表明：(1)在生理钙浓度（2.5µmol/l）下，1日龄和1周龄家兔的离体膀胱条对乙酰胆碱的反应收缩至其最大张力的98%，而8周龄家兔的最大张力为68%；(2)1日龄和1周龄家兔膀胱条的ED50（钙）为0.4 mmol/l，而成年家兔膀胱条的ED50为2.2 mmol/l。(3)新生儿膀胱对地尔硫卓的敏感性明显高于成人膀胱。1µmol/l地尔硫卓显著抑制新生儿膀胱对钙的收缩反应，而8周龄的膀胱在该浓度下无抑制作用。在第二个系列实验中，利用氟化钙FURA-2和表面荧光光谱法，研究了细胞外钙对收缩的影响与细胞内游离钙浓度的相关性。这些研究证实，新生儿膀胱条对钙或胆碱能激动剂的收缩反应增加与细胞内最大游离钙浓度增加有关。
The urinary bladders of 1-day- and 1-week-old rabbits generate higher intravesical pressures in response to bethanechol and field stimulation than bladders isolated from mature 8-week-old rabbits. Yet the density of cholinergic receptors in the rabbit bladder does not change with maturation (1 day to 8 weeks). In an effort to better understand the molecular mechanisms by which newborn rabbit bladders generate greater pressures than the bladders of adult rabbits, we studied the effect of maturation on the relationship between extracellular calcium and contraction. Our results showed quite clearly that (1) at physiologic concentrations of calcium (2.5 µmol/l), isolated bladder strips of 1-day- and 1-week-old rabbits contracted in response to bethanechol to 98% of their maximal tension as opposed to 68% for their 8-week-old counterparts, (2) the ED50(for calcium) for the 1-day and 1-week bladders was 0.4 mmol/l whereas the ED50for the adult bladder strips was 2.2 mmol/l, and (3) the neonatal bladders demonstrated a much greater sensitivity to diltiazem than the adult bladders. The contractile response to calcium of the neonatal bladders was significantly inhibited by 1 µmol/l diltiazem whereas the 8-week-old bladders showed no inhibition at this concentration. In a second series of experiments, the effect of extracellular calcium on contraction was correlated with the intracellular concentration of free calcium using the calcium fluoride FURA-2 and surface spectrofluorometry. These studies confirmed that the increased contractile response of the neonatal bladder strips to calcium or cholinergic agonists was associated with an increase in the maximal intracellular free calcium concentration.