Renal cytosol

Spironolactone antagonizes the effects of aldosterone by binding at the aldosterone receptor in the cytosol of the late distal tubules and renal collecting ducts. Side effects of spironolactone are gynecomastia, decreased Hbido, and impotency. 

Other plasminogen activator inhibitors are PAI-3, which is believed to be identical to the activated protein C inhibitor, and proteinase nexin 1, found in the renal epithelial cells, cytosol of fibroblasts, and cardiac myocytes (37, 42, 44, 45). 

Mistry P, Mastri C, Fowler BA. 1986. Influence of metal ions on renal cytosolic lead-binding proteins and nuclear uptake of lead in the kidney. Biochem Pharmacol 35 711-713. 

Mercuric chloride is a potent nephrotoxicant in the adult rat, but has little effect on the newborn [222], There are significant maturational changes in organ, cellular and subcellular distribution of mercury during the first 4 weeks after birth. With increasing age, mercury is redistributed from the renal cytosolic fraction to the nuclear/mitochondrial fraction, where it may be more damaging. 

Carbonic anhydrase (CA, also called carbonate dehydratase) is an enzyme found in most human tissues. As well as its renal role in regulating pH homeostasis (described below) CA is required in other tissues to generate bicarbonate needed as a co-substrate for carboxylase enzymes, for example pyruvate carboxylase and acetyl-CoA carboxylase, and some synthase enzymes such as carbamoyl phosphate synthases I and II. At least 12 isoenzymes of CA (CA I—XII) have been identified with molecular masses varying between 29 000 and 58 000 some isoenzymes are found free in the cytosol, others are membrane-bound and two are mitochondrial. 

There are many dipeptidases [EC 3.4.13.x]. Cytosol nonspecific dipeptidase [EC 3.4.13.18] (also referred to as peptidase A, glycylglycine dipeptidase, glycylleucine dipeptidase, and A -)3-alanylarginine dipeptidase) catalyzes the hydrolysis of dipeptides. Membrane dipeptidase [EC 3.1.13.19] (also known as microsomal dipeptidase, renal dipeptidase, and dehydropeptidase I) is a zinc-dependent enzyme (a member of the peptidase family M19) that also catalyzes the hydrolysis of dipeptides. 

Renal cytosol and microsomes Ni Ultracentrifugation, Liquid scintillation counting 50)... 

Thiouric acid is formed by XO and is excreted renally. Whereas the cytosolic enzyme TPMT is expressed ubiquitously in humans [e.g., in the intestine, liver, red blood cells (RBC) and white blood cells], XO is not expressed in hematopoietic tissue (94). Therefore, TPMT-dependent methylation is critical in white blood cells, leading to an enhanced cytotoxic effect in patients with low TPMT activity. 

FIGURE 29-5 Effect of aldosterone on renal tubule cells. CO Aldosterone CAD enters the cell and binds to a cytosolic receptor CR], creating an activated hormone-receptor complex CA-R],... 

Transfection efficacy of naked DNA can be increased by physical methods such as electroporation and sonication. Electroporation employs electric pulses to punch holes in the cell membrane, usually smaller than 10 nm but larger than oligonucleotides. With the use of electroporation, DNA was delivered into the cytosol of cells by diffusion. Since its introduction in 1982, in vivo transfection has been achieved in skeletal muscle, fiver, skin, tumors, testis, and the kidney. Tsujie et al. (2001) developed a method to target glomeruli using electroporation in vivo wherein injection of plasmid DNA via the renal artery was followed by application of electric fields. The kidney was electroporated by sandwiching the organ... 

Figure 3. A schematic diagram of the renal proximal tubule showing how the Na+/H+ exchanger, by acidifying tubular fluids, promotes the regeneration of bicarbonate. Interconversions of C02, water, H+, OH and HCOj are catalyzed by carbonic anhydrase (membrane bound and cytosolic).

JAM-1 is a glycoprotein of the IgG superfamily of 43 kDa, one TMD, and two extracellular V-type Ig domains (Martin-Padura et al. 1998). The carboxy terminus is characterized by a PDZ-binding domain, which binds to the PDZ motif of ZO-1 (Hamazaki et al. 2002). Other members of the JAM family have been identified, such as JAM-4, which is expressed in renal glomerular and intestinal epithelial cells, where it was shown to induce Ca2 +-independent intercellular adhesion (Hirabayashi et al. 2003). JAM-1 is further connected to cytosolic... 

In the clinic, esmolol s distribution half-life is 2 min and its elimination half-life is 9 min. Esmolol hydrochloride is rapidly metabolized by hydrolysis of the ester linkage, chiefly by esterases in the cytosol of red blood cells and not by plasma cholinesterases or red cell membrane acetylcholinesterase [22]. Its volume of distribution is 3.4 L kg-1, and its total clearance is 285 mL kg-1 min-1, "... which is greater than cardiac output thus the metabolism ofesmolol is not limited by the rate of blood flow to metabolizing tissues such as the liver or affected by hepatic or renal blood flout [22]. As expected from such a "... high rate of blood-based metabolism, less than 2% of the drug is excreted unchanged in the wind [22]. Within 24 h after infusion, approximately... 

Although calcitriol is synthesized only in the proximal renal tubule, after the administration of pHJcalcidiol, radioactivity in the kidney accumulates only in the distal and collecting tubules. This is the region in which selective resorption of calcium from the urine occurs and, in response to calcitriol, there is induction of calbindin-D28k. As in the intestinal mucosa, calbindin in the kidney is a cytosolic protein and is presumably involved in the intracellular accumulation and transport of calcium. 

Sandoval RM,and Molltorls BA. 2004. Gentamicin traffics retrograde through the secretory pathway and is released in the cytosol via the endoplasmic ret cu um. Am J Physiol Renal Physiol 286 F617-624. 

---