Flores J, Witkum P A, Beckman B, Sharp G W
J Clin Invest. 1975 Aug;56(2):256-62. doi: 10.1172/JCI108088.
The effect of prostaglandin E1 (PGE1) on osmotic water flow across toad bladder and cyclic AMP content of the mucosal epithelial cells has been determined under basal conditions and in the presence of either theophylline or antidiuretic hormone (ADH); Under basal conditions and with PGE1 concentrations from 10(-8) to 10(-5) M no evidence of stimulation of water flow was observed, and with 10(-7) M PGE1 a significant inhibition was foundmcyclic AMP content under control conditions was 8 pmol/mg protein. It was 9 at 10(-8) M PGE1, 13 at 10(-7) M, 16 at 10(-6) M, and 23 at 10(-5) M. In the presence of theophylline, 10(-8) and 10(-7) M PGE1 inhibited the theophylline-induced water flow as expected. In contrast, 10(-6) and 10(-5) M PGE1 enhanced the rate of water flow. Theophylline increased cyclic AMP content from 8 to 18 pmol/mg protein. PGE1 in the presence of theophylline caused marked increases in cyclic AMP content; The content was 23 at 10(-7) M, 41 at 10(-6) M, and 130 at 10(-5) M; Thus PGE1 stimulates theophylline-induced water flow at cyclic AMP concentrations somewhere between 23 and 41 pmol/mg. Further evidence along these lines was obtained from experiments in which the effects of PGE1 on ADH-induced water flow were studied. Inhibitory effects of PGE1 were not observed at concentrations of PGE1 which raised the level of intracellular cyclic AMP to 30 pmol/mg protein or higher. These results were obtained despite the fact that all four concentrations of PGE1 tested were found capable of inhibiting ADH-induced water flow under appropriate conditions or, in other words, were inhibiting the adenylate cyclase controlling water flow, Thus the increase in cyclic AMP content in response to PGE1 is not derived from this enzyme. Thus the stimulation of water flow by PGE1 in the presence of theophylline is thought to be caused by cyclic AMP spilling over from one compartment to the water flow compartment. No evidence was obtained to directly suggest spillover into the sodium transport compartment. Furthermore evidence is discussed to suggest that most of the cyclic AMP generated in the tissue does not originate from the enzyme controlling sodium transport. As cyclic AMP-stimulated water flow and sodium transport are thought to occur in one cell type, the granular cells, distinct pools of cyclic AMP are thought to be present in one and the same cell type. Thus one pool controls water flow and one controls sodium transport. With high concentrations of PGE1 in the presence of theophylline or high concentrations of ADH, the adenylate cyclase responsible for water flow is inhibited; However, PGE1 can stimulate a tissue adenylate cyclase to sufficiently high levels that cyclic AMP spills over into the "water flow compartment" and thus stimulates water flow.
在基础条件下以及存在茶碱或抗利尿激素（ADH）的情况下，已测定前列腺素E1（PGE1）对蟾蜍膀胱跨膜渗透水流以及黏膜上皮细胞中环磷酸腺苷（cAMP）含量的影响。在基础条件下，当PGE1浓度为10⁻⁸至10⁻⁵M时，未观察到对水流有刺激作用的证据，而当PGE1浓度为10⁻⁷M时，发现有显著抑制作用。对照条件下cAMP含量为8 pmol/mg蛋白质。在10⁻⁸M PGE1时为9，在10⁻⁷M时为13，在10⁻⁶M时为16，在10⁻⁵M时为23。在存在茶碱的情况下，10⁻⁸和10⁻⁷M PGE1如预期那样抑制了茶碱诱导的水流。相反，10⁻⁶和10⁻⁵M PGE1提高了水流速率。茶碱使cAMP含量从8 pmol/mg蛋白质增加到18 pmol/mg蛋白质。在存在茶碱的情况下，PGE1使cAMP含量显著增加；在10⁻⁷M时含量为23，在10⁻⁶M时为41，在10⁻⁵M时为130；因此，PGE1在cAMP浓度介于23和41 pmol/mg之间的某个水平刺激茶碱诱导的水流。沿着这些思路的进一步证据来自研究PGE1对ADH诱导的水流影响的实验。当PGE1浓度将细胞内cAMP水平提高到30 pmol/mg蛋白质或更高时，未观察到PGE1的抑制作用。尽管事实上所测试的所有四种PGE1浓度在适当条件下都能抑制ADH诱导的水流，或者换句话说，都能抑制控制水流的腺苷酸环化酶，但仍得到了这些结果。因此，对PGE1反应时cAMP含量的增加并非源自该酶。因此，在存在茶碱的情况下，PGE1对水流的刺激被认为是由cAMP从一个隔室溢出到水流隔室所致。没有获得直接表明溢出到钠转运隔室的证据。此外，有证据表明组织中产生的大部分cAMP并非源自控制钠转运的酶。由于cAMP刺激的水流和钠转运被认为发生在一种细胞类型即颗粒细胞中，所以在同一细胞类型中被认为存在不同的cAMP池。因此一个池控制水流，一个池控制钠转运。在存在茶碱的情况下使用高浓度PGE1或高浓度ADH时，负责水流的腺苷酸环化酶受到抑制；然而，PGE1可刺激组织腺苷酸环化酶达到足够高的水平，以至于cAMP溢出到“水流隔室”，从而刺激水流。
