NO-CGMP INHIBITION OF UROGENITAL SMOOTH MUSCLE

描述(改编自申请人的摘要)：有例外情况 认为肌张力降低代表血管紧张度逆转的范式 激活；降低肌浆钙；失活MLCK和 交叉桥去磷酰化。一氧化氮(NO)是一种普遍存在的神经内分泌， 旁分泌和自分泌抑制信号是已知的松弛血管的信号 通过降低肌浆钙浓度。泌尿生殖器平滑肌 通常有丰富的抑制性神经支配，产生NO。这 应用：NO释放诱导钙离子和交叉桥 松弛的独立活性成分，它内在地加速 内脏平滑肌的缓慢松弛特征。五个具体 目的是(1)表征钙离子非依赖组分 在几种泌尿生殖系统的平滑肌组织中松弛，(2)检验假说 增加cGMP和蛋白激酶G的激活以响应NO是 用放松的活性成分在时间上调节和量化， (3)检验主动松弛是消除闭锁机制的假设 和速度松弛，(4)检验cGMP增加的假设是 时间上调节的和数量上与变化相关的 抑制力量产生的HSP20的磷酸化和(5)测试 假设热休克蛋白20的磷酸化起到细丝“关断”的作用 通过阻止磷酸化的附着物的附着来防止力的产生 十字桥。

DESCRIPTION (Adapted from the Applicant's Abstract): There are exceptions to the paradigm that reductions in smooth muscle tone represent reversal of activation; lowering myoplasmic calcium and inactivation of MLCK and crossbridge dephophorylation. Nitric oxide (NO) is a ubiquitous neuroendocrine, paracrine and autocrine inhibitory signal that is know to relax smooth muscle by lowering the myoplasmic calcium concentration. Urogenital smooth muscles typically have a rich inhibitory innervation which generates NO. This application proposes that NO release induces a calcium-ion and crossbridge independent active component of relaxation which accelerates the inherently slow relaxation characteristic of visceral smooth muscle. The five specific aims are to (1) characterize the calcium ion independent component of relaxation in several urogenital smooth muscle tissues, (2) test the hypothesis that increases in cGMP and activation of protein kinase G in response to NO are temporally regulated and quantitated with the active component of relaxation, (3) test the hypothesis that active relaxation is a mechanism to abolish latch and speed relaxation, (4) test the hypothesis that increases in cGMP are are temporally regulated and quantitatively correlated with changes in phosphorylation of HSP20 that inhibits force generation and (5) test the hypothesis that phosphorylation of HSP20 acts as a thin filament "off switch" that prevents force generation by blocking the attachment of phosphorylated crossbridges.