Tubule proximal

Lead is toxic to the kidney, cardiovascular system, developiag red blood cells, and the nervous system. The toxicity of lead to the kidney is manifested by chronic nephropathy and appears to result from long-term, relatively high dose exposure to lead. It appears that the toxicity of lead to the kidney results from effects on the cells lining the proximal tubules. Lead inhibits the metaboHc activation of vitamin D in these cells, and induces the formation of dense lead—protein complexes, causing a progressive destmction of the proximal tubules (13). Lead has been impHcated in causing hypertension as a result of a direct action on vascular smooth muscle as well as the toxic effects on the kidneys (12,13). 

Hydroxy vitamin D pools ia the blood and is transported on DBF to the kidney, where further hydroxylation takes place at C-1 or C-24 ia response to calcium levels. l-Hydroxylation occurs primarily ia the kidney mitochondria and is cataly2ed by a mixed-function monooxygenase with a specific cytochrome P-450 (52,179,180). 1 a- and 24-Hydroxylation of 25-hydroxycholecalciferol has also been shown to take place ia the placenta of pregnant mammals and ia bone cells, as well as ia the epidermis. Low phosphate levels also stimulate 1,25-dihydtoxycholecalciferol production, which ia turn stimulates intestinal calcium as well as phosphoms absorption. It also mobilizes these minerals from bone and decreases their kidney excretion. Together with PTH, calcitriol also stimulates renal reabsorption of the calcium and phosphoms by the proximal tubules (51,141,181—183). 

The thia2ides are actively secreted into the proximal tubules, where they exert their action on the luminal side of the tubules. The diuretic effect occurs within 1 h after oral adininistration, and the duration of action varies from 4 to 24 h depending on which thia2ide-type diuretic is used. The diuretic effects of the thia2ides are not influenced by acid—base conditions of the blood or urine. Probenecid, which also is secreted into the proximal tubules, may block the diuretic effects of the thia2ides. 

Muzolimine (710), a 1-substituted 2-pyrazolin-5-one derivative, is a highly active diuretic, differing from the structures of other diuretics since it contains neither a sulfonamide nor a carboxyl group. It has a saluretic effect similar to furosemide and acts in the proximal tubule and in the medullary portion of the ascending limb of the loop of Henle. Pharmacokinetic studies in dogs, healthy volunteers and in patients with renal insufficiency show that the compound is readily absorbed after oral administration (B-80MI40406). 

Agents acting in the proximal tubule are seldom used to treat hypertension. Treatment is usually initiated with a thiazide-type diuretic. Chlorthalidone and indapamide are structurally different from thiazides but are functionally related. If renal function is severely impaired (i.e., serum creatinine above 2.5 mg/dl), a loop diuretic is needed. A potassium-sparing agent may be given with the diuretic to reduce the likelihood of hypokalemia. 

AQP7 is expressed in the proximal tubule of the kidney, testis, gastrointestinal tract, immature dendritic cells and ear. This glycerol channel is also highly expressed in adipocytes where it is thought to control the release of triglycerides. 

The kidney contains the major site of renin synthesis, the juxtaglomerular cells in the wall of the afferent arteriole. From these cells, renin is secreted not only into the circulation but also into the renal interstitium. Moreover, the enzyme is produced albeit in low amounts by proximal tubular cells. These cells also synthesize angiotensinogen and ACE. The RAS proteins interact in the renal interstitium and in the proximal tubular lumen to synthesize angiotensin II. In the proximal tubule, angiotensin II activates the sodium/hydrogen exchanger (NHE) that increases sodium reabsorption. Aldosterone elicits the same effect in the distal tubule by activating epithelial sodium channels (ENaC) and the sodium-potassium-ATPase. Thereby, it also induces water reabsotption and potassium secretion. 

OTRs are mainly expressed in myoepithelial cells of the galactiferus channels and the myometrium. The OTRs in vascular endothelial cells, renal epithelial cells (macula densa, proximal tubule) and cardiomyocytes induce the production of NO (vasodilation), natriuresis and release of ANP, respectively. The endometrium, ovary, amnion, testis, epididymis, prostate and thymus also express the OTR supporting a paracrine role of this peptide. Osteoblasts, osteoclasts, pancreatic islets cells, adipocytes, and several types of cancer cells also express OTRs. More over, expression of the OTR... 

Excretion via the kidney can be a straightforward question of glomerular filtration, followed by passage down the kidney tubules into the bladder. However, there can also be excretion and reabsorption across the tubular wall. This may happen if an ionized form within the tubule is converted into its nonpolar nonionized form because of a change in pH. The nonionized form can then diffuse across the tubular wall into plasma. Additionally, there are active transport systems for the excretion of lipophilic acids and bases across the wall of the proximal tubule. The antibiotic penicillin can be excreted in this way. 

Sodium SGLTl -dependent unidirectionai transporter Small intestine and kidney Active uptake of glucose from lumen of intestine and reabsorption of glucose in proximal tubule of kidney against a concentration gradient... 

Stimulation of basolateral Na /H exchanger transport activity in LLC-PK] cells during chronic metabolic acidosis is accompanied by a parallel increase in NHE-1 transcript abundance [80]. Chronic metabolic acidosis also increases the abundance of Na /H exchanger transcripts in rat renal cortices [81] and SV40-transformed mouse proximal tubule cells [82]. 

Renal tubules of rats K liquid membrane micropipet — double-barrel design (valinomycin) K (proximal tubule) 54.4 + 2.5 mM 141 ... 

Proximal tubule cells are exquisitely sensitive to vasculat disturbances and acute tubular necrosis (ATN) can occur naturally in areas of poor perfusion resulting from falling blood pressure, or vasospasm of renal vessels or arterioles. In other words hypoxia associated with partial ischaemia can cause severe damage. It is not then surprising that anoxia associated with iatrogenic, surgically induced total ischaemia produces irreversible damage within a short time unless steps are taken to prevent it. 

The reaction between glucose and protein in the blood produces advanced glycosylation end-products (AGEs), which are metabolized in the proximal tubules. Hyperglycemia increases the synthesis of AGEs in patients with diabetes and the corresponding increase in metabolism is suspected to be a cause of nephropathy associated with diabetes.12... 

Increasing calcium reabsorption from the proximal tubules in the kidney... 

Acute tubular necrosis A form of acute renal failure that results from toxic or ischemic (insufficient oxygen) injury to the cells in the proximal tubule of the kidney. 

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