Park C S, Honeyman T W, Ha S K, Choi H K, Chung C L, Hong C D
Department of Physiology, University of Massachusetts Medical School, Worcester.
J Pharmacol Exp Ther. 1991 Oct;259(1):211-8.
The effects of several ionophores on renin secretion were investigated in rabbit renal cortical slices. When slices were incubated in the absence of Ca++, the K+ ionophore valinomycin (10(-5) approximately 5 x 10(-4) M) or the monovalent cation ionophore nonactin (10(-4) M) stimulated renin secretion about 2-fold. The renin secretion stimulated by valinomycin was further increased by inclusion of the H+ ionophore, carbonylcyanide m-chlorophenylhydrazone. The electroneutral K+/H+ exchange ionophore nigericin (10(-5) approximately 5 x 10(-4) M) stimulated renin secretion in a dose-dependent manner, producing a maximal stimulation of about 17-fold. Another electroneutral exchange ionophore, monensin, also significantly stimulated secretion. The stimulation by both valinomycin and nigericin was apparent whether slices were incubated in Na(+)-rich or K(+)-rich media. The extent of stimulation by the two ionophores was dependent upon the presence of anion with acetate greater than Cl greater than isethionate greater than thiocyanate. Thiocyanate itself markedly inhibited renin secretion. Incubating of slices in an iso-osmotic ammonium acetate medium which is known to induce rapid swelling of secretory granules, stimulated renin secretion to the magnitude comparable to that of maximal stimulation by nigericin in a potassium acetate medium. The pattern of response to these ionophores indicates that changes in K+, H+ and anion gradients across the renin secretory granule may modulate renin secretory rate. It is proposed that conditions which allow accumulation of K+ and anion within acidic renin secretory granules lead to osmotic swelling of the granules and that granule swelling may promote exocytosis.
在兔肾皮质切片中研究了几种离子载体对肾素分泌的影响。当切片在无Ca++的情况下孵育时，K+离子载体缬氨霉素（10(-5)约5×10(-4)M）或单价阳离子离子载体非actin（10(-4)M）可刺激肾素分泌约2倍。通过加入H+离子载体羰基氰化物间氯苯腙，缬氨霉素刺激的肾素分泌进一步增加。电中性K+/H+交换离子载体尼日利亚菌素（10(-5)约5×10(-4)M）以剂量依赖方式刺激肾素分泌，产生约17倍的最大刺激。另一种电中性交换离子载体莫能菌素也显著刺激分泌。无论切片在富含Na(+)或富含K(+)的培养基中孵育，缬氨霉素和尼日利亚菌素的刺激作用均明显。两种离子载体的刺激程度取决于阴离子的存在，乙酸根大于Cl大于羟乙基磺酸根大于硫氰酸根。硫氰酸根本身显著抑制肾素分泌。将切片在已知可诱导分泌颗粒快速肿胀的等渗乙酸铵培养基中孵育，刺激肾素分泌的幅度与在乙酸钾培养基中尼日利亚菌素最大刺激的幅度相当。对这些离子载体的反应模式表明，肾素分泌颗粒跨膜的K+、H+和阴离子梯度变化可能调节肾素分泌速率。有人提出，允许K+和阴离子在酸性肾素分泌颗粒内积累的条件会导致颗粒的渗透性肿胀，并且颗粒肿胀可能促进胞吐作用。
