Kopp Ulla C, Cicha Michael Z, Smith Lori A
Department of Internal Medicine, Department of Veterans Affairs Medical Center, Iowa City 52246, USA.
Am J Physiol Regul Integr Comp Physiol. 2002 Jun;282(6):R1618-27. doi: 10.1152/ajpregu.00701.2001.
Increasing renal pelvic pressure increases afferent renal nerve activity (ARNA) by a PGE(2)-mediated release of substance P (SP) from renal pelvic nerves. The role of cAMP activation in the PGE(2)-mediated release of SP was studied by examining the effects of the adenylyl cyclase (AC) activator forskolin and AC inhibitor dideoxyadenosine (DDA). Forskolin enhanced the bradykinin-mediated release of SP from an isolated rat renal pelvic wall preparation, from 7.3 +/- 1.3 to 15.6 +/- 3.0 pg/min. PGE(2) at a subthreshold concentration for SP release mimicked the effects of forskolin. The EP(2) receptor agonist butaprost, 15 microM, and PGE(2), 0.14 microM, produced similar increases in SP release, from 5.8 +/- 0.8 to 17.0 +/- 2.3 pg/min and from 8.0 +/- 1.3 to 21.6 +/- 2.7 pg/min. DDA blocked the SP release produced by butaprost and PGE(2). The PGE(2)-induced release of SP was also blocked by the PKA inhibitors PKI(14-22) and H-89. Studies in anesthetized rats showed that renal pelvic administration of butaprost, 10 microM, and PGE(2), 0.14 microM, resulted in similar ARNA responses, 1,520 +/- 390 and 1,170 +/- 270%. s (area under the curve of ARNA vs. time) that were blocked by DDA. Likewise, the ARNA response to increased renal pelvic pressure, 7,180 +/- 710%. s, was blocked by DDA. In conclusion, PGE(2) activates the cAMP-PKA pathway leading to a release of SP and activation of renal pelvic mechanosensory nerve fibers.
肾盂压力升高通过PGE(2)介导的肾盂神经中P物质(SP)释放增加肾传入神经活动(ARNA)。通过研究腺苷酸环化酶(AC)激活剂福斯可林和AC抑制剂双脱氧腺苷(DDA)的作用，探讨了cAMP激活在PGE(2)介导的SP释放中的作用。福斯可林增强了缓激肽介导的SP从离体大鼠肾盂壁制剂中的释放，从7.3±1.3 pg/min增加到15.6±3.0 pg/min。低于SP释放阈值浓度的PGE(2)模拟了福斯可林的作用。15 μM的EP(2)受体激动剂布他前列素和0.14 μM的PGE(2)使SP释放产生类似增加，分别从5.8±0.8 pg/min增加到17.0±2.3 pg/min和从8.0±1.3 pg/min增加到21.6±2.7 pg/min。DDA阻断了布他前列素和PGE(2)产生的SP释放。PKA抑制剂PKI(14 - 22)和H - 89也阻断了PGE(2)诱导的SP释放。在麻醉大鼠中的研究表明，肾盂给予10 μM布他前列素和0.14 μM PGE(2)导致类似的ARNA反应，分别为1520±390%·s和1170±270%·s(ARNA与时间曲线下面积)，均被DDA阻断。同样，DDA也阻断了对肾盂压力升高的ARNA反应，即7180±710%·s。总之，PGE(2)激活cAMP - PKA途径，导致SP释放和肾盂机械感觉神经纤维激活。
