Deficiency of fibrinolytic enzyme activities in the serum of patients with Alzheimer-type dementia.

Previously we reported that there is a kallikrein deficiency in the cerebral tissue of patients with Alzheimer-type dementia. The present study was performed to investigate protease changes in the serum of these patients. The results showed that the kallikrein activity was normal, but that the activities of plasmin and urokinase were significantly low. The present findings indicate a derangement in the clotting and fibrinolytic systems in Alzheimer patients.     

Demilune cells of the cat submandibular gland; an unlikely source of kallikrein

The functional significance of kallikrein in the salivary gland remains unclear partially because of uncertainty over its precise cellular localization. Kallikrein was thought to originate in acinar cells, until recent evidence from cat and rat localized it primarily to the ducts. The possibility that salivary kallikrein may also be located in demilune cells was investigated in this study. - The total kallikrein content of cat submandibular glands was found to be substantially reduced by sampathetic nerve stimulation; whereas parasympathetic stimulation had no significant effect. These biochemical findings did not correlate with morphological studies that revealed almost complete depletion of the demilune cells secretory granules after stimulation of either division of the autonomic nerve supply. This lack of correlation makes it unlikely that kallikrein is present in the demilune cell secretory granules.     

Demilune cells of the cat submandibular gland; an unlikely source of kallikrein

Summary The functional significance of kallikrein in the salivary gland remains unclear partially because of uncertainty over its precise cellular localization. Kallikrein was thought to originate in acinar cells, until recent evidence from cat and rat localized it primarily to the ducts. The possibility that salivary kallikrein may also be located in demilune cells was investigated in this study. — The total kallikrein content of cat submandibular glands was found to be substantially reduced by sampathetic nerve stimulation; whereas parasympathetic stimulation had no significant effect. These biochemical findings did not correlate with morphological studies that revealed almost complete depletion of the demilune cells secretory granules after stimulation of either division of the autonomic nerve supply. This lack of correlation makes it unlikely that kallikrein is present in the demilune cell secretory granules.Acknowledgment. This study is made possible through the Dean's MRC grant number MD-3489 to the College of Dentistry, University of Saskatchewan.Authors wish to thank Mr. D. Duncan, Dept. of Oral Biology and D. Mandeville of Medical Photographic Services for technical assistance.     

Effects of kallidinogenase on urinary kallikrein excretion and plasma prostanoid concentrations in patients with essential hypertension

The effects of kallidinogenase on urinary kallikrein excretion, plasma immunoreactive prostanoids and platelet aggregation were investigated in patients with essential hypertension. Urinary kallikrein excretion and plasma 6-keto PGF1 alpha concentration were significantly decreased in these patients. Significant decreases in blood pressure, as well as significant increases of urinary kallikrein excretion and plasma 6-keto PGF1 alpha concentration after kallidinogenase administration were also observed.     

The localization of kallikrein in the dog and guinea-pig submandibular glands

Summary In the dog and guinea-pig submandibular glands kallikrein seems to be present in the striated duct cells. Following sympathetic nerve and in vivo isoproterenol stimulation of the dog and guinea-pig submandibular gland respectively, there is a reduction of kallikrein concentration. Ultrastructurally this reduction corresponds to the decrease of straited duct secretory granules in both species. Parasympathetic stimulation also causes some release of kallikrein from both species.Supported by Dean's M.R.C. grant to the College of Dentistry.     

Release of renal kallikrein to the perfusate by isolated rat kidney

Summary The addition of furosemide to the fluid used to perfuse isolated rat kidney increases the kallikrein activity found in the perfusion fluid. The experiments favour the concept that furosemide activates a kallikrein precursor or/and the synthesis and release of kallikrein in the kidneys.     

Localization of renal kallikrein in the dog

Summary Renal kallikrein was estimated in glomerular, tubular and medullary fractions of dog kidneys. It was found primarily in the cortex, the highest level of activity being detected in a glomeruli-rich fraction. These results support previous observation that kallikrein may be associated with the juxta-glomerular complex.     

Relationship between the renal kallikrein activity and the urinary excretion of kallikrein in rats

Summary Adrenalectomy reduces, and sodium depletion increases, both the daily urinary excretion of kallikrein and the kallikrein activity in the renal cortex. These 2 variables were found to correlate significantly in normal, sodium depleted and adrenalectomized rats, thus supporting the view that kallikrein excretion reflects the activity of the enzyme in the kidney.Acknowledgments. This word was supported by the Deutsche Forschungsgemeinschaft. The technical assistance of Mrs G. Breypohl and Ms J. Kopatsch is gratefully acknowledged. Dr M. Marin-Grez was a fellow of the Alexander von Humbodt Foundation and Dr G. Bönner of the Deutsche Forschungsgemeinschaft.     

Potentiation by crude kallikrein of the myotropic effect of angiotensin I in the isolated rabbit aortic strip.

Crude kallikrein (Padutin), but not pure kallikrein, when preincubated with angiotensin I caused a potentiation of the myotropic effect of decapeptide on the isolated continuously superfused rabbit aortic strip. Addition of converting enzyme inhibitor, SQ 20881, to the medium inhibited this potentiation. The potentiation by crude kallikrein of the myotropic effect of angiotensin I is probably due to the conversion of decapeptide to octapeptide angiotensin II. This study indicates that Padutin is not a pure kallikrein preparation and probably contains a kininase fraction which causes the conversion of angiotensin I.     

Acyl-kallikrein; a delivery system for the kinin-liberating enzyme

Summary Glandular kallikrein can be temporarily acylated at the active centre by 4-amidinophenyl benzoates. The time course of reactivation depends on the nature of the acyl group introduced. Benzoyl kallikrein was used as a delivery system for kallikrein in vivo. In rabbits, bolus injection of the acylated enzyme caused a long-lasting drop in blood pressure due to sustained kinin liberation.     

Acyl-kallikrein; a delivery system for the kinin-liberating enzyme

Glandular kallikrein can be temporarily acylated at the active centre by 4-amidinophenyl benzoates. The time course of reactivation depends on the nature of the acyl group introduced. Benzoyl kallikrein was used as a delivery system for kallikrein in vivo. In rabbits, bolus injection of the acylated enzyme caused a long-lasting drop in blood pressure due to sustained kinin liberation.     

Effects of kallidinogenase on urinary kallikrein excretion and plasma prostanoid concentrations in patients with essential hypertension

Summary The effects of kallidinogenase on urinary kallikrein excretion, plasma immunoreactive prostanoids and platelet aggregation were investigated in patients with essential hypertension. Urinary kallikrein excretion and plasma 6-keto PGF₁ concentration were significantly decreased in these patients. Significant decreases in blood pressure, as well as significant increases of urinary kallikrein excretion and plasma 6-keto PGF₁ concentration after kallidinogenase administration were also observed.     

Localization of renal kallikrein in the dog

Renal kallikrein was estimated in glomerular, tubular and medullary fractions of dog kidneys. It was found primarily in the cortex, the highest level of activity being detected in glomeruli-rich fraction. These results support previous observation that kallikrein may be associated with the juxta-glomerular complex.     

Deficiency of kallikrein-like enzyme activities in cerebral tissue of patients with Alzheimer's disease.

We examined the changes in the intracerebral activities, at the time of postmortem autopsy, in patients with Alzheimer's disease. When compared with the control group, the activity of kallikrein-like enzyme was significantly decreased, while prolyl endopeptidase activity increased, in the patients group. Aprotinin inhibited 50% of the activity of the former enzyme at 2 x 10(-7) M. Taken together with the results of a multivariate study, the above findings may indicate that intracerebral kallikrein deficiency plays an important role in the pathogenesis of Alzheimer's disease.     

Inhibition of the ureteral contractions induced by rat urine with kallikrein antibodies

Summary Purified urinary kallikrein induces contractions of the rat ureter in vitro. Antibodies against kallikrein block the contractile response of the isolated ureter to rat urine.This work was supported by the Deutsche Forschungsgemeinschaft (SFB 90). The technical assistance of J. Kopatsch, R. Marpoder and H. Seeger is gratefully acknowledged.     

Deficiency of kallikrein-like enzyme activities in cerebral tissue of patients with alzheimer's disease

Summary We examined the changes in the intracerebral activities, at the time of postmortem autopsy, in patients with Alzheimer's disease. When compared with the control group, the activity of kallikrein-like enzyme was significantly decreased, while prolyl endopeptidase activity increased, in the patients group. Aprotinin inhibited 50% of the activity of the former enzyme at 2×10^–7M. Taken together with the results of a multivariate study, the above findings may indicate that intracerebral kallikrein deficiency plays an important role in the pathogenesis of Alzheimer's disease.     

Effect of nerve stimulation,denervation, and duct ligation,on kallikrein content and duct cell granules of the cat's submandibular gland

Summary Various procedures which reduce or deplete the kallikrein content of the cat's submandibular gland correspondingly reduce the number of apical granules in the striated duct cells. The kallikrein content is greatly reduced after chronic parasympathetic but not after sympathetic nerve section which suggests that the parasympathetic innervation is required for synthesis or storage of this enzyme.We wish to acknowledge the valuable assistance of Dr T. Nihei and Mr. J. Wimal in some of the enzyme measurements.This work was supported by grants from the Medical Research Council of Canada and the Alberta Heart Foundation.     

Potentiation by crude kallikrein of the myotropic effect of angiotensin I in the isolated rabbit aortic strip

Summary Crude kallikrein (Padutin^®), but not pure kallikrein, when preincubated with angiotensin I caused a potentiation of the myotropic effect of decapeptide on the isolated continuously superfused rabbit aortic strip. Addition of converting enzyme inhibitor, SQ 20881, to the medium inhibited this potentiation. The potentiation by crude kallikrein of the myotropic effect of angiotensin I is probably due to the conversion of decapeptide to octapeptide angiotensin II. This study indicates that Padutin is not a pure kallikrein preparation and probably contains a kininase fraction which causes the conversion of angiotensin I.The authors are greatful to Prof. G. L. Haberland, Bayer AG, Elberfeld (BRD), for his generous gift of pure Kallikrein^® KZC 1/75; to Bayer, Leverkusen (BRD), for Padutin^® and to Squibb, New Jersey, USA, for SQ 20881. This work is supported in part by Eczacibai Research Foundation, Levent, Istanbul, Turkey. The technical assistance of Mr. M. Kabaçam is greatly appreciated.     

Inhibition of the ureteral contractions induced by rat urine with kallikrein antibodies

Purified urinary kallikrein induces contractions of the rat ureter in vitro. Antibodies against kallikrein block the contractile response of the isolated ureter to rat urine.     

Hydrolysis of histones by horse urinary kallikreins

Summary Horse urinary kallikrein was shown to hydrolyze histones from calf thymus and chicken nuclei erythrocytes. The hydrolysis is inhibited by benzamidine and hyposulfite but not by soy-bean trypsin inhibitor; horse plasma kallikrein also produces this hydrolysis.Work supported by grants from Projeto BIOQ/FAPESP (São Paulo), FINEP (Rio) and CNPq (Rio).Fellow from CNPq, from Instituto Biológico (São Paulo).