Clyman R I, Blacksin A S, Sandler J A, Manganiello V C, Vaughan M
J Biol Chem. 1975 Jun 25;250(12):4718-21.
In term gestational human umbilical artery segments incubated in room air at 37 degrees, histamine, acetylcholine, bradykinin, K+, and serotonin (agonists that cause contraction) cause accumulation of guanosine 3':5'-monophosphate (cGMP) without altering the content of adenosine 3':5'-monosphophate (cAMP); prostaglandin E1 (PGE1), which relaxes the artery, causes cAMP accumulation without affecting the cGMP content (Clyman, R. I., Sandler, J.A., Manganiello, V.C., and Vaughan, M. (1975) J. Clin. Invest., in press). It has been postulated that Ca-2+ is important in the regulation of cyclic nucleotides in other tissues. In the umbilical artery the control of cAMP content by PGE1 was independent of Ca-2+. After incubation in Ca-2+-free medium, the c GMP contentof the artery segments was decreased by 50% and was unaffected by histamine, acetylcholine, bradykinin, and K+. Readdition of Ca-2+ (2.7 mM) or Sr-2+ (3.6 mM) to the medium partially restored the basal cGMP content and the agonist effects on the cGMP content. However, Sr-2+ was not as effective as Ca-2+ in this regard. Ionophores A23187 and X537A (agents that facilitate Ca-2+ movement through membranes) mimicked the effects of these Ca-2+-dependent agonists on cGMP content. Incubation with the phosphodiesterase inhibitor 3-isobutyl-1-methyl xanthine (0.1 mM) increased both the basal content of cGMP and the histamine-induced accumulation 3-fold. This effect was dependent on the presence of Ca-2+ also. Accumulation of cGMP induced by serotonin, on the other hand, was not diminished in Ca-2+-depleted arteries and, in fact, seemed to be inhibited by 2.7 mM Ca-2+. These observations are consistent with the existence in the umbilical artery of two separate mechanisms for control of cGMP synthesis that are influenced differently by Ca-2+.
在37摄氏度的室温空气中孵育的足月妊娠人脐动脉段，组胺、乙酰胆碱、缓激肽、钾离子和5-羟色胺（引起收缩的激动剂）会导致鸟苷3':5'-单磷酸（cGMP）积累，而不会改变腺苷3':5'-单磷酸（cAMP）的含量；能使动脉舒张的前列腺素E1（PGE1）会导致cAMP积累，而不影响cGMP含量（克莱曼，R.I.，桑德勒，J.A.，曼加尼罗，V.C.，和沃恩，M.（1975年）《临床研究杂志》，即将发表）。据推测，钙离子在其他组织中对环核苷酸的调节很重要。在脐动脉中，PGE1对cAMP含量的控制与钙离子无关。在无钙离子的培养基中孵育后，动脉段的cGMP含量降低了50%，且不受组胺、乙酰胆碱、缓激肽和钾离子的影响。向培养基中重新添加钙离子（2.7毫摩尔）或锶离子（3.6毫摩尔）可部分恢复基础cGMP含量以及激动剂对cGMP含量的影响。然而，在这方面锶离子不如钙离子有效。离子载体A23187和X537A（促进钙离子通过细胞膜的试剂）模拟了这些依赖钙离子的激动剂对cGMP含量的影响。用磷酸二酯酶抑制剂3-异丁基-1-甲基黄嘌呤（0.1毫摩尔）孵育可使基础cGMP含量和组胺诱导的积累增加3倍。这种作用也依赖于钙离子的存在。另一方面，5-羟色胺诱导的cGMP积累在缺钙的动脉中并未减少，事实上，似乎受到2.7毫摩尔钙离子的抑制。这些观察结果与脐动脉中存在两种不同的cGMP合成控制机制一致，这两种机制受钙离子的影响不同。
