cGMP mediates corpus cavernosum smooth muscle relaxation with altered cross-bridge function

被引:22
作者
Chuang, AT [1 ]
Strauss, JD
Steers, WD
Murphy, RA
机构
[1] Univ Virginia, Hlth Sci Ctr, Dept Urol, Charlottesville, VA 22908 USA
[2] Univ Virginia, Hlth Sci Ctr, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA
关键词
penile erection; nitric oxide; cGMP; cross-bridge phosphorylation; smooth muscle; erectile dysfunction;
D O I
10.1016/S0024-3205(98)00259-8
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
We tested the prevailing paradigm that relaxation of corpus cavernosum smooth muscle (CCSM) and penile erection depends upon nitric oxide-induced elevation of myoplasmic cGMP and reduced Ca2+-dependent myosin regulatory light chain phosphorylation levels. This hypothesis invokes a reversal of normal activation pathways. Upon stimulation with 250 mu M phenylephrine, phosphorylation of the 20 kD myosin regulatory light chains of rabbit or human CCSM increased approximately 4-fold coincident with contraction. Removal of the agonist was followed by a slow reduction in cross-bridge phosphorylation and force to basal levels. The NO donor, sodium nitroprusside elicited a dose-dependent increase in tissue [cGMP] associated with a rapid relaxation in the continued presence of phenylephrine, although cross-bridge phosphorylation remained significantly elevated. Thus the NO-cGMP inhibitory pathway in CCSM is not simply a reversal of excitatory signal transduction mechanisms. An unidentified mechanism contributes to relaxation by decreasing the rate of cross-bridge recruitment through phosphorylation.
引用
收藏
页码:185 / 194
页数:10
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