Secretory system

M. Chrispeels, Sorting of proteins in the secretory system. Annu. Rev. Plant Phv.siol. 42 21 (1991). 

Unwanted effects of sulfonamide-type diuretics (a) hypokalemia is a consequence of excessive 1C loss in the terminal segments of the distal tubules where increased amounts of Na are available for exchange with 1C (b) hyperglycemia and glycosuria (c) hyper-uricemia-increase in serum urate levels may precipitate gout in predisposed patients. Sulfonamide diuretics compete with urate for the tubular organic anion secretory system. 

Combination with probenecid. Renal elimination of penicillin occurs chiefly via the anion (acid)-secretory system of the proximal tubule (-COOH of 6-APA). The acid probenecid (p. 316) competes for this route and thus retards penicillin eUmination ... 

These active secretory systems are important in drug excretion because charged anions and cations are often strongly bound to plasma proteins and therefore are not readily available for excretion by filtration. However, since the protein binding is usually reversible, the active secretory systems can rapidly and efficiently remove many protein-bound drugs from the blood and transport them into tubular fluid. 

Thiazide diuretics act in the distal convoluted tubule, where they block Na -Cl cotransport (Fig. 21.4). The Na" -Cl cotransport takes place on the luminal surface of distal convoluted tubules. Thus, to exert their diuretic action, the thiazides must reach the luminal fluid. Since the thiazide diuretics are largely bound to plasma proteins and therefore are not readily filtered across the glomeruli, access to the luminal fluid is accomplished by the proximal tubule organic acid secretory system. The drugs then travel along the nephron, presumably being concentrated as fluid is abstracted, until they reach their site of inhibitory action in the distal convoluted tubule. 

Orally administered thiazides are rapidly absorbed from the gastrointestinal tract and begin to produce diuresis in about 1 hour. Approximately 50% of an oral dose is excreted in the urine within 6 hours. These compounds are organic acids and are actively secreted into the proximal tubular fluid by the organic acid secretory mechanism. There also appears to be an extrarenal pathway for their elimination involving the hepatic-biliary acid secretory system that is particularly important for thiazide elimination when renal function is impaired. 

The loop diuretics must be present in the tubular fluid before they can become effective. Because of their extensive binding to plasma proteins, filtration across the glomerular capillaries is restricted. Like the thiazides, however, the loop diuretics are weak organic acids that are substrates for the organic acid secretory system in the proximal tubule. A consequence of this active secretion is that the presence of other organic acids or certain forms of renal disease may impair the therapeutic usefulness of the loop diuretics. 

When probenecid (ColBENEMID) is given in sufficient amounts, it will block the active reabsorption of uric acid in the proximal tubules following its glomerular filtration, thereby increasing the amount of urate eliminated. In contrast, low dosages of probenecid appear to compete preferentially with plasma uric acid for the proximal tubule anionic transport system and thereby block its access to this active secretory system. The uricosuric action of probenecid, however, is accounted for by the drug s ability to inhibit the active reabsorption of filtered urate. 

VirD4 and VirB together constitute a type IV secretory system required for the transfer of T-DNA and several other Vir proteins, such as VirE2 and VirF. VirD4 may act to promote the interaction between the T-DNAA irD2 complex with the VirB-encoded secretion apparatus. There are a total of 11... 

VirB Part of secretory system required for T-DNA transfer... 

Organic acid secretory systems are located in the middle third of the straight part of the proximal tubule (S2 segment). These systems secrete a variety of organic acids (uric acid, nonsteroidal anti-inflammatory drugs [NSAIDs], diuretics, antibiotics, etc) into the luminal fluid from the blood. These systems thus help deliver diuretics to the luminal side of the tubule, where most of them act. Organic base secretory systems (creatinine, choline, etc) are also present, in the early (Si) and middle (S2) segments of the proximal tubule. 

All thiazides are secreted by the organic acid secretory system in the proximal tubule and compete with the secretion of uric acid by that system. As a result, thiazide use may blunt uric acid secretion and elevate serum uric acid level. 

Two tubular secretory systems exist for the active transport of organic acids and organic bases. Many xenobiotics can find their way back into the blood via these routes. 

The main factor in determining whether or not a drug or poison will be excreted via the urinary tract is its lipophilicity. If the material is lipophilic it can be reabsorbed by passive diffusion. The glomerular filtration rate, individual tubule secretory systems, and tubule exchange systems will help to establish excretion rates. Because a molecule s lipophilicity can be pH-dependent the acidity of the urine is extremely important. 

Lin JH, Los LE, Ulm EH, et al. Kinetic studies on the competition between famotidine and cimetidine in rats. Evidence of multiple renal secretory systems for organic cations. Drug Metab Dispos 1988 16 52-56. 

Mature 11S globulins are hexameric proteins that are initially assembled and transported through the secretory system as intermediate trimers. In the protein storage vacuole, the subunits of these trimers are proteolytically processed to yield... 

Pharmacokinetics The drugs are effective orally. Most thiazides take 1 to 3 weeks to produce a stable reduction in blood pressure, and they exhibit a prolonged biological half-life (40 hours). All thiazides are secreted by the organic acid secretory system of the kidney (see p. 224). 

Correct answer = B. Thiazide decreases the excretion of uric aid by the acid secretory system. Hypokalemia is the most frequently encountered adverse effect of thiazide treatment. Chlorothiazide may induce hyperglycemia and hypotension. 

Excretion The primary route of excretion is through the organic acid (tubular) secretory system of the kidney (see p. 224), as well as by glomerular filtration. Patients with impaired renal function must have dosage regimens adjusted. Thus the Xyz of penicillin G can increase from a normal of 1/2 -1 hour to 10 hours in individuals with renal failure. Probenecid inhibits the secretion of penicillins. Nafcillin is primarily eliminated through the biliary route. [Note This is also the preferential route for the acylureido penicillins in cases of renal failure.]... 

Uricosurics, such as probenecid or benz-bromarone (100 mg/day), promote renal excretion of uric acid. They saturate the organic acid transport system in the proximal renal tubules, making it unavailable for urate reabsorption. When underdosed, they inhibit only the acid secretory system, which has a smaller transport capacity. Urate elimination is then inhibited and a gout attack is possible. In patients with urate stones in the urinary tract, uricosurics are contraindicated. 

Diseases and disorders involving the lacrimal system are among the more common conditions experienced by ophthalmic patients, with as many as 25% complaining of dry eye symptoms alone.The lacrimal system is most easily considered as having three components—the secretory system, the distribution system, and the excretory or drainage system.These components must work in harmony to support a healthy, moist, and comfortable ocular surfece. 

Figure 24-3 Cross-section of the lacrimal secretory system. See text for products of the labeled basal secretors. (Adapted from Botelho SY. Tears and the lacrimal gland. Sci Am 1964 211 78-85. Copyright 1964 by Scientific American, Inc. All rights reserved.)...

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