Sims S M, Ho N F, Geary T G, Thomas E M, Day J S, Barsuhn C L, Thompson D P
Upjohn Laboratories, Kalamazoo, MI 49001, USA.
Int J Parasitol. 1996 Jan;26(1):25-35. doi: 10.1016/0020-7519(95)00113-1.
To determine if a cuticle microenvironment pH is maintained by adult Haemonchus contortus, organic acid excretion kinetics and absorption kinetics of selected model weak acids and a weak base were measured in incubation media that varied in buffer capacity (0.25-20 mM HEPES or 5 mM glycine) and initial pH (7.5 or 3.5). To evaluate the importance of the cuticle as a pathway for organic acid excretion and drug absorption the pharynx was paralyzed with 1 nM ivermectin. H. contortus changed the media pH from initial values of 7.5 or 3.25 to an asymptotic value of approximately 5.6. The rate of pH change depended on the buffer capacity, but was not affected by chemical ligation with ivermectin. The intrinsic rate of excretion of organic acids (0.045 +/- 0.016 micromol/cm2 x h) was constant during the first 8-12 h of incubation and was independent of initial pH, buffer capacity or ivermectin ligation. The rates of absorption of the model weak acids, benzoic acid and p-nitrophenol, and the model weak base, aniline, were not affected by initial pH, buffer capacity or ivermectin ligation. These results suggest that H. contortus excretes organic acid endproducts of carbohydrate metabolism across its cuticle, and that these acids maintain a microenvironment pH within the water-filled pores of the cuticle that controls the rate of adsorption of weakly acidic or basic drugs.
为了确定捻转血矛线虫成虫是否能维持角质层微环境的pH值，我们在缓冲能力（0.25 - 20 mM HEPES或5 mM甘氨酸）和初始pH值（7.5或3.5）不同的孵育培养基中，测量了选定的模型弱酸和弱碱的有机酸排泄动力学和吸收动力学。为了评估角质层作为有机酸排泄和药物吸收途径的重要性，用1 nM伊维菌素使咽麻痹。捻转血矛线虫将培养基的pH值从初始值7.5或3.25改变为约5.6的渐近值。pH值变化的速率取决于缓冲能力，但不受伊维菌素化学连接的影响。在孵育的最初8 - 12小时内，有机酸的固有排泄速率（0.045±0.016 μmol/cm²·h）是恒定的，并且与初始pH值、缓冲能力或伊维菌素连接无关。模型弱酸苯甲酸和对硝基苯酚以及模型弱碱苯胺的吸收速率不受初始pH值、缓冲能力或伊维菌素连接的影响。这些结果表明，捻转血矛线虫通过其角质层排泄碳水化合物代谢的有机酸终产物，并且这些酸在角质层充满水的孔隙内维持微环境pH值，该pH值控制弱酸性或碱性药物的吸附速率。
