Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The luminal membrane of collecting duct cells, specially the intercalated cells, is normally exposed to active kallikrein. This is due to the specific localization of renal kallikrein in the connecting tubule cells. We have previously reported inhibition of distal bicarbonate secretion by renal kallikrein. The present study was performed to evaluate the participation of basolateral Cl-/HCO3- exchanger and luminal H(+)-ATPase activity of cortical collecting duct segments (CCD) in the mechanism involved in the inhibition of bicarbonate secretion induced by the enzyme. The effect of orthograde injections of 1 microgram/ml (250 U/6.3 mg) pig pancreatic kallikrein, in the absence and presence of 1 mM DIDS (stilbene-disulfonic acid) in the renal tubule system, was evaluated. Urine fractions were collected after two-minutes stop-flow. Changes in the urine fraction (Fr) related to those in free-flow urine samples (Ff) were related to the respective polyfructosan (Inutest) ratio. Renal kallikrein activity (Fr:Ff kallikrein/Fr:Ff polyfructosan) increased significantly in the first 120 microliters urine fraction collected after glandular 1 microgram/ml kallikrein, P < 0.05, (first stop-flow) and after glandular 1 microgram/ml kallikrein plus 1 mM. DIDS P < 0.05 (second stop flow). Bicarbonate secretion rate (Fr:Ff HCO3-/Fr:Ff polyfructosan) of collecting ducts was significantly reduced in the first 120 microliters urine fraction collected, related to control, during the first and second stop-flow periods. No difference was shown in bicarbonate excretion between the first 120 microliters urine fractions collected after administration of glandular kallikrein and glandular kallikrein plus DIDS. To measure H(+)-ATPase activity, rat microdissected cortical collector tubules (CCD) were incubated in the presence of increasing glandular kallikrein doses (A: 93, B: 187 and C: 375 mU/200 microL) in the presence of ouabain (4 microM) and omeprazole (100 microM) to inhibit Na(+)-K(+)-ATPase and H(+)-K(+)-ATPase, respectively. In CCD, bafilomycin-sensitive H(+)-ATPase activity (pmol/mm/min) after increasing kallikrein doses did not differ significantly from control. No difference related to control H(+)-ATPase activity was observed when microdissected CCD segments were incubated in the presence of an AT1 receptor antagonist (Losartan 10(-6) M) and glandular kallikrein (93 mU). On the contrary, angiotensin II (10(-8) M) significantly decreased H(+)-ATPase activity. The present study shows that neither basolateral Cl-/HCO3- exchanger nor H(+)-ATPase activity are involved in bicarbonate inhibition by glandular kallikrein at CCD. Involvement of luminal Cl-/HCO3- exchanger at beta intercalated cells in CCD may be suggested for the bicarbonate secretion inhibition induced by renal kallikrein.
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PMID:Effect of glandular kallikrein on distal bicarbonate transport. Role of basolateral Cl-/HCO3- exchanger and vacuolar H(+)-ATPase. 1090 41

We investigated the role of the kallikrein-kinin system in cardiac function and glucose utilization in the streptozotocin (STZ)-induced diabetic rat model using a gene transfer approach. Adenovirus harboring the human tissue kallikrein gene was administered to rats by intravenous injection at 1 week after STZ treatment. Human kallikrein transgene expression was detected in the serum and urine of STZ-induced diabetic rats after gene transfer. Kallikrein gene delivery significantly reduced blood glucose levels and cardiac glycogen accumulation in STZ-induced diabetic rats. Kallikrein gene transfer also significantly attenuated elevated plasma triglyceride and cholesterol levels, food and water intake, and loss of body weight gain, epididymal fat pad, and gastrocnemius muscle weight in STZ-induced diabetic rats. However, these effects were blocked by icatibant, a kinin B2 receptor antagonist. Cardiac function was significantly improved after kallikrein gene transfer as evidenced by increased cardiac output and +/-delta P/delta t (maximum speed of contraction/relaxation), along with elevated cardiac sarco(endo)plasmic reticulum (Ca2+ + Mg2+)-ATPase (SERCA)-2a, phosphorylated phospholamban, NOx and cAMP levels, and GLUT4 translocation into plasma membranes of cardiac and skeletal muscle. Kallikrein gene delivery also increased Akt and glycogen synthase kinase (GSK)-3beta phosphorylation, resulting in decreased GSK-3beta activity in the heart. These results indicate that kallikrein through kinin formation protects against diabetic cardiomyopathy by improving cardiac function and promoting glucose utilization and lipid metabolism.
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PMID:Kallikrein gene delivery improves serum glucose and lipid profiles and cardiac function in streptozotocin-induced diabetic rats. 1585 48

Considering the growing importance of the interaction between components of kallikrein-kinin and renin-angiotensin systems in physiological and pathological processes, particularly in diabetes mellitus, the aim of the present study was to investigate the interaction between angiotensin-(1-7) (Ang-(1-7)) and bradykinin (BK), important components of these systems in an insulin resistance model of diabetes, and the effect of insulin on it. For this the response of mesenteric arterioles of anesthetized neonatal streptozotocin-induced (n-STZ) diabetic and control rats was evaluated using intravital microscopy. Though capable of potentiating BK in non-diabetic rats, Ang-(1-7) did not potentiate BK in n-STZ rats. Chronic but not acute insulin treatment restored the potentiation. This restorative effect of insulin was abolished by a K+ channel blocker (tetraethylammonium), by nitric oxide synthase inhibitor (N-nitro-L-arginine methyl ester) and by a cyclooxygenase inhibitor (indomethacin). On the other hand, Na(+)-,K(+)-ATPase inhibition (by ouabain) did not abolish the effect of insulin. There was no difference in mRNA and protein expression of B1 and B2 kinin receptor subtypes between n-STZ diabetic and control rats. Insulin treatment did not alter the kinin receptor expression. Our data allow us to conclude that diabetes impaired the interaction between BK and Ang-(1-7) and that insulin restores it. The restoring effect of insulin depends on membrane hyperpolarization, nitric oxide release and cyclooxygenease metabolites but not Na+K+-ATPase. Alteration of kinin receptor expression might not be involved in the restoring effect of insulin on the potentiation of BK by Ang-(1-7).
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PMID:Lack of potentiation of bradykinin by angiotensin-(1-7) in a type 2 diabetes model: role of insulin. 1740 6

Water and solute transport in the efferent ducts and epididymis are important for the establishment of the appropriate luminal environment for sperm maturation and storage. Aquaporin 9 (AQP9) is the main water channel in the epididymis, but its regulation is still poorly understood. Components of the kinin-kallikrein system (KKS), leading to the production of bradykinin (BK), are highly expressed in the lumen of the male reproductive tract. We report here that the epididymal luminal fluid contains a significant amount of BK (2 nM). RT-PCR performed on epididymal epithelial cells isolated by laser capture microdissection (LCM) showed abundant BK type 2 receptor (Bdkrb2) mRNA expression but no type 1 receptor (Bdkrb1). Double-immunofluorescence staining for BDKRB2 and the anion exchanger AE2 (a marker of efferent duct ciliated cells) or the V-ATPase E subunit, official symbol ATP6V1E1 (a marker of epididymal clear cells), showed that BDKRB2 is expressed in the apical pole of nonciliated cells (efferent ducts) and principal cells (epididymis). Triple labeling for BDKRB2, AQP9, and ATP6V1E1 showed that BDKRB2 and AQP9 colocalize in the apical stereocilia of principal cells in the cauda epididymidis. While uniform Bdkrb2 mRNA expression was detected in the efferent ducts and along the epididymal tubule, marked variations were detected at the protein level. BDKRB2 was highest in the efferent ducts and cauda epididymidis, intermediate in the distal initial segment, moderate in the corpus, and undetectable in the proximal initial segment and the caput. Functional assays on tubules isolated from the distal initial segments showed that BK significantly increased AQP9-dependent glycerol apical membrane permeability. This effect was inhibited by BAPTA-AM, demonstrating the participation of calcium in this process. This study, therefore, identifies BK as an important regulator of AQP9.
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PMID:Segmental expression of the bradykinin type 2 receptor in rat efferent ducts and epididymis and its role in the regulation of aquaporin 9. 1882 5

The chronic hyperglycemia measured alongside diabetes development is associated with significant long-term damage and failure of various organs. In the present study it was shown that hyperglycemia induced early and long term increases in nitric oxide (NO) levels, kallikrein activity and vascular capillary permeability measured as plasma extravasation, and decreases of Na/K ATPase activity in diabetic rat retina 4 and 12 weeks after streptozotocin (STZ) injection. Treatment of the animals for 5 consecutive days with a novel selective bradykinin B(1) receptor (BKB(1)-R) antagonist R-954 (2mg/kg s.c) at the end of the 4 and 12 week periods highly reduced NO, kallikrein and capillary permeability and increased Na/K ATPase activity in the retina. These results suggest that the BKB(1)-R receptor subtype is over-expressed during the streptozotocin-induced development of diabetes in rat retina as evidenced by the inhibitory effects of the BKB(1)-R antagonist R-954 on NO, kallikrein and vascular permeability increases as well as Na/K ATPase decreases. The beneficial role of the BKB(1)-R antagonist R-954 for the treatment of the diabetic retinopathy is also suggested.
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PMID:Blockade of early and late retinal biochemical alterations associated with diabetes development by the selective bradykinin B1 receptor antagonist R-954. 2236 20

Inactivation of the tissue kallikrein gene in mice impairs renal handling of potassium due to enhanced H, K-ATPase activity, and induces hyperkalemia. We investigated whether the R53H loss-of-function polymorphism of the human tissue kallikrein gene affects renal potassium handling. In a crossover study, 30 R53R homozygous and 10 R53H heterozygous healthy males were randomly assigned to a low-sodium/high-potassium or a high-sodium/low-potassium diet to modulate tissue kallikrein synthesis. On the seventh day of each diet, participants were studied before and during a 2-h infusion of furosemide to stimulate distal potassium secretion. Urinary kallikrein activity was significantly lower in R53H than in R53R subjects on the low-sodium/high-potassium diet and was similarly reduced in both genotypes on high-sodium/low-potassium. Plasma potassium and renal potassium reabsorption were similar in both genotypes on an ad libitum sodium/potassium diet or after 7 days of a high-sodium/low-potassium diet. However, the median plasma potassium was significantly higher after 7 days of low-sodium/high-potassium diet in R53H than in R53R individuals. Urine potassium excretion and plasma aldosterone concentrations were similar. On the low-sodium/high-potassium diet, furosemide-induced decrease in plasma potassium was significantly larger in R53H than in R53R subjects. Thus, impaired tissue kallikrein stimulation by a low-sodium/high-potassium diet in R53H subjects with partial tissue kallikrein deficiency highlights an inappropriate renal adaptation to potassium load, consistent with experimental data in mice.
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PMID:Partial genetic deficiency in tissue kallikrein impairs adaptation to high potassium intake in humans. 2376 Feb 92


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