Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To understand the role of the kallikrein-kinin system in the kidney all components of the system and their localization need to be considered. About half the kallikrein in urine occurs as the proenzyme which arises in the distal tubule. Kinins are formed in the distal tubule and collecting duct from urokinnogen which is found throughout the tubule. Urine contains about twice as much lysyl-brandykinin as bradykinin. A third kinin, methionyl-lysyl-bradykinin, also can occur in urine. It is probably produced by uropepsin as the kinin is largely formed in acidified urine and its formation is inhibited by pepstatin. The significance of the three kinins is unknown. Kinins are normally slowly (few hours) destroyed in urine. The importance of kallikrein, urokinogen and kininases in regulating the level of kinins needs to be determined.
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PMID:The kallikrein-kinin system in the kidney. 21 52

The glandular kininogenase kallikrein is known to occur in many mammalian organs and glands but direct histochemical localization has been achieved in only a few cases. We have now been able to localize porcine kallikrein in the acinar cells of the pancreas and in the striated and collecting duct cells of the submandibular gland. Incubation of frozen and fixed sections with one of the crossreacting antibodies, anti-pancreatic, anti-submandibular or anti-urinary kallikrein IgG resulted in the same immunofluorescence pattern. There was evidence of a specific fluorescence neither in the acinar cells, nor in the interstitial tissue or blood cells of the submandibular gland nor in the islets of Langerhans, the interlobular ducts or blood vessels of the pancreas. From all data now available about glandular kallikreins, it seems that the kallikreins in these organs are very similar.
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PMID:Localization of kallikrein in porcine pancreas and submandibular gland as revealed by the indirect immunofluorescence technique. 34 94

Kallikrein excreted with the urine appears to be formed in the kidney. The kallikrein-kinin system in the kidney is localized in the distal nephron from the juxtaglomerular apparatus to the collecting duct. It has been shown that intrarenal infusion of kinins produces an increase in renal blood flow as well as diuresis and natriuresis. Part of the effect of kinins appears to be mediated by the release of prostaglandins. However, the precise role of the renal kallikrein-kinin system in sodium and volume homeostasis and in blood pressure regulation still remains to be determined. Mineralocorticoids as well as the diuretics furosemide, bumetanide and bendroflumethiazide increase, spironolactone decreases kallikrein excretion. Urinary kallikrein has been shown to increase acid-as well as cryoactivation of prorenin in vitro. It is unclear as yet, however, whether the renal kallikrein-kinin system takes part in converting inactive prorenin into active renin in vivo. There are reports on subnormal, normal as well as increased kallikrein excretion in spontaneously hypertensive rats. In rats susceptible to the hypertensive effect of salt a substantially decreased excretion of kallikrein has been observed. Kallikrein excretion has been described to be increased in primary aldosteronism and to be reduced in a proportion of patients with established essential hypertension. In patients with labile hypertension, however, kallikrein excretion appears to be normal suggesting that decreased urinary kallikrein in essential hypertension is a consequence rather than a cause of hypertension. The renal kallikrein-kinin system does not appear to play a primary role in the pathogenesis of hypertension.
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PMID:[Renal kallikrein-kinin system and control of blood pressure (author's transl)]. 39 77

The distribution of kallikrein in dog kidneys was studied. It was found that kallikrein decreased from the outer to the inner cortex and that the medulla and papilla had very little kallikrein. The site of kallikrein secretion in the nephron was also studied by performing stop-flow techniques in dogs. The highest kallikrein concentration was found in the fractions with the lowest sodium concentration. It was concluded that kallikrein is secreted into the urine at the level of the distal tubule by either the tubule itself or by a structure related to this part of the nephron. In addition, the possible involvement of the kallikrein-kinin system in the regulation of sodium excretion was investigated. Circulating kinins and urinary kallikrein were increased in saline-loaded dogs. Urinary kallikrein also increased in dogs that have "escaped" the sodium-retaining effect of desoxycorticosterone. Experiments in rats with different sodium intake showed a relationship between water and sodium excretion and urinary kallikrein. These data suggest that the kallikrein-kinin system could participate in the regulation of the renal function at the level of the distal tubule or collecting duct.
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PMID:Renal kallikrein: its localization and possible role in renal function. 124 53

Renal kallikrein is synthetized in the distal nephron and secreted in urine. Studies on the microdissected nephron and on the whole kidney using immunohistochemistry indicate that kallikrein is produced at the level of the distal part of the distal tubule and in some species in the cells of the initial part of the collecting duct. Urinary kinins are formed at these same sites. The renal tubule contains high levels of kininases, able to inactivate kinins, but the kininases are located mainly up-stream the sites of kinin production, i.e. in the glomerulus and in the proximal tubule. A kininase activity is however also found in the medullary collecting duct. This collecting duct kininase activity might contribute to the control of kinin levels in kidney and urine. The physiological role of the renal kallikrein kinin system is not completely understood. There is some evidence for a role of urinary kinins in water and solute transferrence in the distal nephron. Also kinin production in the renal interstitium and/or circulation may contribute to the control of renal blood flow. In the isolated perfused rat kidney vasoconstricted by angiotensin II for example, the high molecular weight kininogen is hydrolyzed to release kinins and induces a vasodilatation. The kallikrein-kinin system therefore might play a role in kidney function by antagonizing the vascular effect of angiotensin II in the renal circulation and the maintenance renal blood flow.
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PMID:[Kallikrein-kinin system, the kidney and arterial pressure]. 283 86

Tissue kallikrein (E.C. 3.4.21.35) and arginine esterase A, another closely related, kinin-generating serine protease, have been localized by immunocytochemistry in rat kidney, using monoclonal antibodies that do not crossreact with other kallikrein-related enzymes or with tonin. Kallikrein was present primarily in the apical cytoplasm of the connecting tubule and the cortical collecting duct. Esterase A, on the other hand, was present primarily in the basolateral region of both proximal and distal straight tubules in the outer medulla and medullary rays. In addition, esterase A was demonstrable in distal convoluted tubules and, to a lesser extent, in proximal convoluted tubules. The presence of different kinin-generating enzymes at these sites would permit the formation of kinins from appropriate substrates on both the vascular and luminal poles of separate segments of the kidney tubule.
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PMID:Comparison of the distribution of tissue kallikrein and esterase A, a kallikrein-like enzyme, in rat kidney using specific monoclonal antibodies. 341 6

The influence of fixation on the immunocytochemical localization of tissue kallikrein in the kidney has been evaluated using both monoclonal and polyclonal antibodies. These studies have provided several results relevant to kallikrein localization in kidney: (1) the intensity and distribution of immunostaining with both polyclonal and monoclonal anti-kallikrein antibodies is fixation-dependent; (2) the most intense and consistent localizations of kallikrein are in the connecting tubule and the cortical collecting duct of the nephron; (3) kallikrein-like immunoreactivity is seen in proximal tubules with polyclonal but not with non-cross-reactive monoclonal antibodies; and (4) fixatives which disrupt membranes reveal a kallikrein-like antigen in straight tubules of the outer medulla. However, immunostaining with monoclonal antibodies indicates that much of the observed immunostaining at this site probably represents cross-reactivity with another member of the kallikrein family of enzymes.
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PMID:Rat urinary kallikrein localization in kidney: effects of fixation. 344 57

A synthetic substrate for kallikrein, pro-phe-arg-naphthylester, was used in order to identify histochemically kallikrein-like enzyme-containing segments of the nephron in the rat kidney. The localization was technically facilitated by comparing sections histochemically incubated with neighbouring freeze-dried sections and by semiquantitative evaluation of the enzyme activity performed. In the proximal tubules, the enzyme activity increased from the first segment to the third segment which exhibited the most pronounced activity encountered. In the proximal convoluted tubules the enzyme activity was present mainly in the deep half of the cortex. This was generally weaker in the other segments of the nephron where enzyme activity was present. In the descending thin limb of Henle, weak activity was noticed in a few initial segments. However, in the ascending thick limb of Henle, more pronounced enzyme activity was shown. In the macula densa, the distal convoluted tubule and the collecting duct, very weak activity was observed in a few segments. Below the demarcation between the outer stripe and the inner stripe of the medulla, no enzyme activity was noticed. This is the first description of the exact tubular localizations of kallikrein-like enzyme activity in the nephron.
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PMID:Segmental localization of kallikrein-like pro-phe-arg-naphthylester esterase in the rat nephron. 655 Apr 57

The anatomical relationship between kallikrein and renin in the rat kidney was investigated immunohistochemically by the peroxidase-antiperoxidase method. Kallikrein was localized to the convoluted distal tubule, starting at a point, distal to the juxtaglomerular apparatus, where the thick ascending limb of loop of Henle transformed into the convoluted distal tubule. The thick ascending limb was identified by its content of uromucoid (Tamm-Horsfall glycoprotein). Kallikrein was never observed within the juxtaglomerular apparatus itself. The kallikrein-containing tubule ended where the distal tubule submerged into the collecting duct. Renin was found in epitheloid cells of the afferent arteriole. When neighboring sections were stained for kallikrein and renin, respectively, no close anatomical relationship was observed between the kallikrein-containing and the renin-containing structures.
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PMID:Localization of kallikrein in the rat kidney and its anatomical relationship to renin. 703 45

The luminal membrane of collecting duct cells, especially the intercalated cells, is normally exposed to active kallikrein. This is the consequence of the specific localization of this renal enzyme in the connecting tubule cells and its principal route of secretion being into the tubular lumen. It is conceivable that kallikrein acts downstream on a transporter involved in distal bicarbonate handling. To investigate this possibility, we estimated bicarbonate concentration and measured kallikrein amidolytic activity in urine fractions collected after a classical stop-flow experiment in rabbits. A highly significant inverse correlation was found between these parameters (r = -0.94, p < 0.001) in the peak kallikrein fractions. Neither sodium nor potassium concentration were correlated to kallikrein. This suggests that the physiological role of renal kallikrein may be to regulate extracellular fluid pH by inhibiting collecting duct bicarbonate secretion. To test the hypothesis that tubular fluid kallikrein activity and bicarbonate secretion are causally related, we developed a novel in vivo stop-flow injection model ('orthograde stop-flow'). A hog-kallikrein containing solution (0.5 microgram/ml) was injected through the abdominal aorta into the renal tubular system of one kidney of barbiturate-anesthetized rats, while the renal blood supply was interrupted. The ureter was then occluded and renal blood perfusion reinitiated. After a 2-min contact time five 125-microliters urine fractions were collected. Bicarbonate secretion was clearly detected in the second and third fractions (i.e. those coming from the collecting ducts) of the control animals, which had received only the vehicle. There was no bicarbonate secretion peak in the corresponding urine fractions collected from kallikrein-injected animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evidence for an inhibitory effect of kallikrein on collecting duct bicarbonate secretion in rats and rabbits. 753 9


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