Sugawara M, Hashimoto K, Ota Z
Third Department of Internal Medicine, Okayama University Medical School, Japan.
Am J Physiol. 1988 Jun;254(6 Pt 2):R863-9. doi: 10.1152/ajpregu.1988.254.6.R863.
The involvement of prostaglandin E2 (PGE2), adenosine 3',5'-cyclic monophosphate (cAMP), and vasopressin in lithium-induced polyuria was investigated in rats. Administration of LiCl (4 mmol/kg body wt) for 7 days induced a marked polyuria with a significant excretion of urinary PGE2. Administration of indomethacin (IND, 5 mg/kg body wt) for 4 days to lithium-induced diabetes insipidus (LiDI) rats diminished urine volume by 80% and urinary PGE2 by 85%. The in vitro data of the intact rat kidney showed that lithium stimulated arginine vasopressin (AVP)-induced PGE2 production and suggested that PGE2 suppressed cAMP synthesis in rat renal medulla. The AVP-induced PGE2 synthesis was greater and the AVP-stimulated cAMP production lower in the LiDI rat kidney in vitro. Interference of the vasopressin-associated cAMP system and the increased PGE2 synthesis in the kidney may be involved in the development of LiDI. The reduced cAMP production in the LiDI rat kidney might be partly due to the increased PGE2 synthesis. In LiDI rats plasma vasopressin increased, whereas AVP concentration in the hypothalamus and the neurohypophysis significantly decreased. It is postulated that lithium stimulates vasopressin release from the central nervous system and that elevated plasma vasopressin potentiates PGE2 production in the kidney synergistically with lithium.
在大鼠中研究了前列腺素E2（PGE2）、腺苷3',5'-环磷酸（cAMP）和血管加压素在锂诱导的多尿中的作用。给予LiCl（4 mmol/kg体重）7天可诱导显著的多尿，并伴有尿PGE2的大量排泄。对锂诱导的尿崩症（LiDI）大鼠给予吲哚美辛（IND，5 mg/kg体重）4天，尿量减少80%，尿PGE2减少85%。完整大鼠肾脏的体外数据表明，锂刺激精氨酸血管加压素（AVP）诱导的PGE2生成，并提示PGE2抑制大鼠肾髓质中的cAMP合成。在体外，LiDI大鼠肾脏中AVP诱导的PGE2合成更多，而AVP刺激的cAMP生成更低。血管加压素相关的cAMP系统的干扰以及肾脏中PGE2合成的增加可能参与了LiDI的发生发展。LiDI大鼠肾脏中cAMP生成减少可能部分归因于PGE2合成增加。在LiDI大鼠中，血浆血管加压素增加，而下丘脑和神经垂体中的AVP浓度显著降低。据推测，锂刺激中枢神经系统释放血管加压素，且升高的血浆血管加压素与锂协同增强肾脏中PGE2的生成。
