Churchill P C, McDonald F D, Churchill M C
J Pharmacol Exp Ther. 1979 Dec;211(3):615-9.
Phenytoin stimulated renin secretion from rat renal cortical slices. A sigmoid relationship was found between stimulatory effect and log concentration, from 1 to 8 mg/100 ml. The ED5C was 2.8 mg/100 ml. Basal secretion and the stimulation of secretion elicited by phenytoin were blocked by incubating slices in a K-free medium and by adding 1 mM ouabain to the medium (both of which inhibit Na,K-adenosine triphosphatase activity and increase intracellular Na concentration), and by reductions in the Na concentration of the incubation medium. NaCl in the incubation medium was replaced by choline chloride so that osmolality and Cl concentration were held constant. It is suggested that renin secretion rate is directly related to the transmembrane Na gradient, that phenytoin stimulates secretion by increasing the gradient, and that ouabain, K-free medium and reductions in Na concentration of the medium inhibit secretion by reducing the gradient.
苯妥英可刺激大鼠肾皮质切片分泌肾素。在浓度为1至8毫克/100毫升时,刺激作用与对数浓度之间呈S形关系。半数有效浓度(ED5C)为2.8毫克/100毫升。通过在无钾培养基中孵育切片、向培养基中添加1毫摩尔哇巴因(二者均可抑制钠钾-腺苷三磷酸酶活性并增加细胞内钠浓度)以及降低孵育培养基中的钠浓度,可阻断基础分泌和苯妥英引起的分泌刺激。将孵育培养基中的氯化钠替换为氯化胆碱,以使渗透压和氯浓度保持恒定。提示肾素分泌速率与跨膜钠梯度直接相关,苯妥英通过增加该梯度来刺激分泌,而哇巴因、无钾培养基以及培养基中钠浓度的降低则通过降低该梯度来抑制分泌。