Willenbucher R F, Xie Y N, Eysselein V E, Snape W J
Department of Medicine, Harbor-University of California, Los Angeles, Medical Center, Torrance 90502.
Am J Physiol. 1992 Jan;262(1 Pt 1):G159-64. doi: 10.1152/ajpgi.1992.262.1.G159.
Photolytic release of free adenosine 3',5'-cyclic monophosphate (cAMP) from its caged form was used to evaluate the physiological role of several proposed mechanisms of cAMP-mediated relaxation of circular smooth muscle in the distal rabbit colon. Photolysis of caged cAMP produced a rapid relaxation of bethanechol-contracted distal circular muscle strips that was dependent on ultraviolet exposure time. An increase in release of free cAMP, associated with increased ultraviolet exposure, was confirmed with high-performance liquid chromatography. Vanadate (an ATPase inhibitor) (3 mM) caused a 48% decrease in cAMP-mediated relaxation, while ouabain and a zero K+ bath solution failed to affect relaxation. cAMP-mediated relaxation of KCl-contracted strips was significantly less effective than that of bethanechol-contracted strips. Although this finding suggested that cAMP-mediated relaxation may involve K+ channel modulation, specific (glibenclamide, charybdotoxin) and nonspecific (TEA) K+ channel blockade failed to affect cAMP-mediated relaxation of bethanechol-contracted strips. The photolytic release of cAMP failed to relax Ca(2+)-contracted saponin skinned muscle strips. These studies suggest 1) modulation of Ca2+ pumps plays an important role in this model of relaxation of distal colonic circular muscle in the rabbit colon, 2) modulation of the Na+ pump or sarcolemmal K+ channels may not play an important physiological role in relaxation induced by a rapid rise in intracellular cAMP, and 3) cAMP does not seem to have a significant physiological effect on the Ca2+ sensitivity contractile apparatus.
利用光解作用从其笼形形式释放游离的3',5'-环磷酸腺苷（cAMP），来评估几种提出的cAMP介导的兔结肠远端环形平滑肌舒张机制的生理作用。笼形cAMP的光解作用使由氨甲酰甲胆碱收缩的远端环形肌条迅速舒张，该舒张作用依赖于紫外线照射时间。高效液相色谱法证实，随着紫外线照射增加，游离cAMP的释放量也增加。钒酸盐（一种ATP酶抑制剂）（3 mM）使cAMP介导的舒张作用降低了48%，而哇巴因和零钾浴液未能影响舒张作用。cAMP介导的氯化钾收缩条的舒张作用明显不如氨甲酰甲胆碱收缩条的舒张作用有效。尽管这一发现表明cAMP介导的舒张作用可能涉及钾通道调节，但特异性（格列本脲、蝎毒素）和非特异性（四乙铵）钾通道阻断剂均未能影响氨甲酰甲胆碱收缩条的cAMP介导的舒张作用。cAMP的光解作用未能使钙收缩的皂角苷去皮肌条舒张。这些研究表明：1）钙泵的调节在兔结肠远端环形肌舒张模型中起重要作用；2）钠泵或肌膜钾通道的调节在细胞内cAMP快速升高诱导的舒张过程中可能不发挥重要的生理作用；3）cAMP似乎对钙敏感性收缩装置没有显著的生理影响。
