Sato I, Murota S
Department of Physiological Chemistry, Graduate School, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Japan.
Life Sci. 1995 Feb 17;56(13):1079-87. doi: 10.1016/0024-3205(95)00044-7.
We explored whether endothelium-derived nitric oxide (EDNO) acts in an autocrine or paracrine fashion to activate the soluble guanylate cyclase by measuring the elevations of cGMP levels. Comparisons were made between two culture models in which EDNO can stimulate cGMP synthesis within the same cells (endothelial cells) where it is formed, or in the neighboring cells (smooth muscle cells). The basal amount of EDNO showed no difference in cGMP levels when the endothelial cells (EC) were cultured either alone (iso-culture) or together with the smooth muscle cells (SMC, co-culture). However, cGMP levels were synergistically increased by the BK-stimulated EDNO when EC were co-cultured with SMC. The synergistical increase was significantly inhibited by 3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186), an extracellular radical scavenger. These findings suggest that the tonic formed basal EDNO has an autocrine effect on cGMP levels of EC themselves. In contrast, BK-stimulated phasic formed EDNO has not only an autocrine effect, but also a paracrine effect on cGMP levels of EC themselves and the adjacent SMC.
我们通过测量环磷酸鸟苷（cGMP）水平的升高，探究内皮源性一氧化氮（EDNO）是否以自分泌或旁分泌方式激活可溶性鸟苷酸环化酶。在两种培养模型之间进行了比较，在一种模型中，EDNO可在其产生的同一细胞（内皮细胞）内刺激cGMP合成，在另一种模型中，EDNO可在相邻细胞（平滑肌细胞）中刺激cGMP合成。当内皮细胞（EC）单独培养（同型培养）或与平滑肌细胞（SMC，共培养）一起培养时，基础量的EDNO在cGMP水平上没有差异。然而，当EC与SMC共培养时，BK刺激产生的EDNO可使cGMP水平协同升高。这种协同升高被细胞外自由基清除剂3-甲基-1-苯基-2-吡唑啉-5-酮（MCI-186）显著抑制。这些发现表明，持续性产生的基础EDNO对EC自身的cGMP水平具有自分泌作用。相比之下，BK刺激产生的阶段性EDNO不仅对EC自身的cGMP水平具有自分泌作用，而且对相邻的SMC的cGMP水平具有旁分泌作用。
