Stier C T, Manning M, Sawyer W H
J Pharmacol Exp Ther. 1980 Mar;212(3):412-7.
Substitution of the amino acid glycine for 7-proline in oxytocin produces an analog, [7-glycine]oxygocin, having markedly reduced antidiuretic and vasopressor activities but retaining considerable natriuretic activity. We administered this analog alone and with distally acting diuretic agents to test the hypothesis that oxytocin and its analogs decrease proximal tubular fluid reabsorption. If [7-glycine]oxytocin shares a common mechanism of action with any of these agents, the response to combined treatment should be less than additive, otherwise, the saluretic effect of both agents should be maintained. Subcutaneous administration of [7-glycine]oxytocin, 10 micrograms/kg, to conscious fluid-loaded rats produced a natriuresis, diuresis and kaliuresis. Hydrochlorothiazide and [7-glycine]oxytocin administered together to the same rats had a greater than additive effect on urine volume and sodium excretion. Furosemide and [7-glycine]oxytocin had an additive effect on urine volume, sodium and chloride excretion. Triamterene blocked the kaliuresis caused by [7-glycine]oxytocin, although the two agents administered together had a greater than additive effect on sodium excretion. These results indicate that [7-glycine]oxytocin does not share a common natriuretic mechanism or site of action with the above diuretics. Our data are consistent with the hypothesis that oxytocin and its analogs may increase urinary sodium excretion by decreasing net proximal tubular fluid reabsorption.
在催产素中，用氨基酸甘氨酸替代7位的脯氨酸会产生一种类似物，即[7-甘氨酸]催产素，其抗利尿和升压活性显著降低，但仍保留相当大的利钠活性。我们单独给予这种类似物以及与作用于远曲小管的利尿剂联合使用，以检验催产素及其类似物可减少近端肾小管液重吸收这一假说。如果[7-甘氨酸]催产素与这些药物中的任何一种具有共同的作用机制，那么联合治疗的反应应小于相加效应，否则，两种药物的利钠效应应得以维持。给清醒的、负荷液体的大鼠皮下注射10微克/千克的[7-甘氨酸]催产素，会产生利钠、利尿和排钾作用。将氢氯噻嗪和[7-甘氨酸]催产素一起给予同一些大鼠，对尿量和钠排泄的作用大于相加效应。呋塞米和[7-甘氨酸]催产素对尿量、钠和氯排泄具有相加效应。氨苯蝶啶可阻断[7-甘氨酸]催产素引起的排钾作用，尽管两种药物一起使用对钠排泄的作用大于相加效应。这些结果表明，[7-甘氨酸]催产素与上述利尿剂不具有共同的利钠机制或作用部位。我们的数据与催产素及其类似物可能通过减少近端肾小管液的净重吸收来增加尿钠排泄这一假说相符。
