Santos-Neto M S, Carvalho A F, Forte L R, Fonteles M C
Divisão de Farmacologia Renal e Metabólica, Unidade de Pesquisas Clínicas, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, CE, Brasil.
Braz J Med Biol Res. 1999 Aug;32(8):1015-9. doi: 10.1590/s0100-879x1999000800012.
Guanylin and uroguanylin are peptides that bind to and activate guanylate cyclase C and control salt and water transport in many epithelia in vertebrates, mimicking the action of several heat-stable bacteria enterotoxins. In the kidney, both of them have well-documented natriuretic and kaliuretic effects. Since atrial natriuretic peptide (ANP) also has a natriuretic effect mediated by cGMP, experiments were designed in the isolated perfused rat kidney to identify possible synergisms between ANP, guanylin and uroguanylin. Inulin was added to the perfusate and glomerular filtration rate (GFR) was determined at 10-min intervals. Sodium was also determined. Electrolyte dynamics were measured by the clearance formula. Guanylin (0.5 microg/ml, N = 12) or uroguanylin (0.5 microg/ml, N = 9) was added to the system after 30 min of perfusion with ANP (0.1 ng/ml). The data were compared at 30-min intervals to a control (N = 12) perfused with modified Krebs-Hanseleit solution and to experiments using guanylin and uroguanylin at the same dose (0.5 microg/ml). After previous introduction of ANP in the system, guanylin promoted a reduction in fractional sodium transport (%TNa+, P<0.05) (from 78.46 +/- 0.86 to 64.62 +/- 1.92, 120 min). In contrast, ANP blocked uroguanylin-induced increase in urine flow (from 0.21 +/- 0.01 to 0.15 +/- 0.007 ml g-1 min-1, 120 min, P<0.05) and the reduction in fractional sodium transport (from 72.04 +/- 0. 86 to 85.19 +/- 1.48, %TNa+, at 120 min of perfusion, P<0.05). Thus, the synergism between ANP + guanylin and the antagonism between ANP + uroguanylin indicate the existence of different subtypes of receptors mediating the renal actions of guanylins.
鸟苷林和尿鸟苷林是一类肽，它们能与鸟苷酸环化酶C结合并激活该酶，调控脊椎动物多种上皮组织中的盐和水转运，其作用类似于几种热稳定细菌毒素。在肾脏中，它们都有明确的利钠和利钾作用。由于心房利钠肽（ANP）也具有由环磷酸鸟苷（cGMP）介导的利钠作用，因此设计了在离体灌注大鼠肾脏的实验，以确定ANP、鸟苷林和尿鸟苷林之间可能存在的协同作用。向灌注液中加入菊粉，并每隔10分钟测定一次肾小球滤过率（GFR）。同时也测定钠含量。通过清除率公式测量电解质动力学。在用ANP（0.1 ng/ml）灌注30分钟后，向系统中加入鸟苷林（0.5 μg/ml，N = 12）或尿鸟苷林（0.5 μg/ml，N = 9）。每隔30分钟将数据与用改良Krebs-Hanseleit溶液灌注的对照组（N = 12）以及使用相同剂量（0.5 μg/ml）鸟苷林和尿鸟苷林的实验进行比较。在系统中预先加入ANP后，鸟苷林促使钠分数转运（%TNa+）降低（P<0.05）（从78.46±0.86降至64.62±1.92，120分钟）。相反，ANP阻断了尿鸟苷林诱导的尿流量增加（从0.21±0.01降至0.15±0.007 ml g-1 min-1，120分钟，P<0.05）以及钠分数转运的降低（在灌注120分钟时，从72.04±0.86升至85.19±1.48，%TNa+，P<0.05）。因此，ANP + 鸟苷林之间的协同作用以及ANP + 尿鸟苷林之间的拮抗作用表明存在介导鸟苷林肾脏作用的不同亚型受体。
