浙江大学医学院：《药理学 Pharmacology》课程教学资源（PPT课件）利尿药 Diuretics

Diuretics Huifang Tang(汤慧芳) tanghuifang@zju.edu.cn Dept Pharmacology, Schoolof Medicine Zhejiang University

Diuretics Huifang Tang (汤慧芳) tanghuifang@zju.edu.cn Dept. Pharmacology, Schoolof Medicine , Zhejiang University

The Kidney: Kidneys Excretion of water ions, and toxic metabolites Balance in electrolytes water. and acid-base in the boe Ur Bladde

Overview Excretion in the kidney 1. Solutes(溶质) Blood with Clean blood 1)工 ons(electrolytes) wastes 2)Organic anions(weak acids) and organic cations(weak bases 3)Other solutes 2. Water Glomerulus Glomerular filtration Wastes(urine) to the bladder Tubule secretion and In the nephron(left), reabsorption tiny blood vessels intertwine with urine Tubule collecting tubes. Each kidney contains about Nephron I million nephrons

Proximal NaHcO3 Nacl Nacl (+PTH) Distal convoluted convoluted tubule Proximal 6570%Na straight tubule 10%Na+ ca Collecting Glomerulus H2o tubule Cortex 325%N ()NaCl 2~5%Na+ 2C| K H Thick ascending limb HO urine Thi (+ADH) descend limb Collecting concentration duct Thin ascending limb Loop of Henle nner medulla

urine concentration

d. Excretion of inorganic ion 2 3 4 5 6 7 对流扩散简单扩散通道介导载体介导ATP介导同向转运反向转运 的扩散 的扩散 的转运 CCC AAA A AAAA AA ΦΦ東 C CCCC BB 细胞膜 CC AA B BBB H2O ATP A ADP A A 三种不同JA 蛋白介导的转运 的离子1B 原发主动转运继发主动转运 被动转运 [主动转运 1:对流扩散,溶于水中的离子借助于水流排出细胞外;2:简单扩散,为脂溶性物 质进入细胞的方式;3:通道介导的扩散,离子通过蛋白构成的孔道(通道)顺电化 学梯度进入细胞,通道开闭受电压、化学物质和机械力等的门控;4:载体介导的扩 散,离子在载体蛋白的帮助下,顺膜内外电化学梯度进行转运;5:ATP介导的转运, 以ATP水解提供能量,离子逆膜内外电化学梯度进行转运;6同向转运,在主动转 运一种离子的同时,带动另一种离子作同方向转运;7:反向转运,在主动转运一种 离子的同时,带动另一种离子作反方向转运

1. Excretion of inorganic ion

2. Excretion of organic ion 管腔膜细胞管周膜 管腔膜细胞管周膜 K+ K+ K+ K ATP酶 1)ATP酶 Na Na+ Na (2同向转运体反向转运体(2 KG aKG 易化扩散 )4(3反向转运体反向转运体(3 易化扩散 A C 有机酸 有机碱 近曲小管有机酸和有机碱分泌 1:原发性主动转运;2:继发性主动转运;3:三次主动转运;A=:有机 酸;C:有机碱;aKG2:Q-朝戊二酸或其他二羧酸

2. Excretion of organic ion

Pro×ma| convoluted tubule(近曲小管) ATP结合盒转运体( ATP-binding cassette transporter,ABC转运体) Pgp m邮燃12次跨膜结构 MRP1/2/3/6 CDITTt-FDT0ETmmm 17次跨膜结构 ATP ATP MRP4/5 uun2次跨膜结构 COOH 6次跨膜结构 溶质载体类转运体( solute carrier,SLC) 有机阴离子转运体家族( organic anion transporter,oAT) 有机阳离子转运体家族( organIc cation transporter,OCT) 寡肽转运体( oligopeptide transporter,PEPT 核苷转运体( nucleoside transporter,NT)

Proximal convoluted tubule (近曲小管)

3. Excretion of h2o AQP有通透水分子的特殊构型。 例如,AQP1的N-和C末端均 在细胞内,由6个跨膜区和5个 袢(A~E)组成,B和E样有HN b 天冬酰胺脯氨酸丙氨酸(NPA) 结构,该两个袢在细胞膜形成 COOH 水孔道,形状类似于“砂漏 E ( hourglass)”;四个AQPl 分子组成四聚体结构,其中 个AQP1分子的细胞外部分有 个长的多糖链。 H2N HOOC Water excretion Water channels or aquaporins(AQPs) AQPO-AQP12

3. Excretion of H2O

distal convoluted tubule connecting glomerulus、 tubule 汤 Vr AQP2 Water 4 AQP3 cortex proximal AQP1 tubule AQP4 AQP7 +ADh Water outer stripe Water I outer medulla inner stripe descending Water k thin limb collecting ducts inner medulla Wi ascendin +ADh Water thin lim final urine

Luminal spc e AQP3 or AQP4 Exocytosis Protein Kinase a ATP CAMP SesAC ADH antidiuretic A0P2s的w如HnEG Gas AOP ormone 抗利尿激素 Gas V2R Nudeus ADH Othe AQP3 Synthesis Endocytosis AQP3 or AQP4 Function and modulation of AQP2 and AQP3 Collecting tubule cells

Collecting tubule or AQP4 or AQP4