Inhibition of peptic activity by carbenoxolone and glycyrrhetinic acid

Henman, F D

doi:10.1136/gut.11.4.344

Cited by 37 publications

(12 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several types of anti-pepsin agents, such as sucralfate, carbenoxolone and pepstatin, are known to act on the en zyme directly, and their mechanisms of action have been reported (16)(17)(18)(19); sucralfate in its suspension form ad sorbs pepsin at pH's above 3 (16); carbenoxolone inhibits the peptic activity of purified pepsin by forming an insolu ble complex (17,18); pepstatin is bound to an equimolar amount of pepsin to inactivate the enzyme without form ing precipitates (19). Thus, the mechanism of the anti-pep tic activity of ecabet shown in the present study seems to be different from the activities of these agents.…”

Section: Discussionmentioning

confidence: 99%

Altered Vasoconstrictor Responsiveness in Vitamin D-Induced Arteriosclerotic Rat Aortas

Ito

Nakamura

Onoda

et al. 1993

Japanese Journal of Pharmacology

View full text Add to dashboard Cite

ABSTRACT-To investigate the mechanism of the anti-peptic action of ecabet sodium (TA-2711) observed in pylorus-ligated rats, effects of this drug on the peptic activity of rat gastric juice, purified hog pepsin and pepsinogen were studied in vitro. After incubation with or without ecabet at acidic pH, the reaction mixture was centrifuged, and the peptic activity of the supernatant was measured. Ecabet depressed the peptic activ ity of pepsin and pepsinogen in parallel with a decrease in the protein concentration of the respective super natant. Depression was greatest with pepsinogen (97% at 2.5 mg/ml of the drug) followed by gastric juice (about 60% at 10 mg/ml), and inhibition of the peptic activity of pepsin was weakest (about 10% at 10 mg/ml). When a fraction of the rat gastric juice containing substances with molecular weights below 10,000 was added to the pepsin solution, the anti-peptic activity of ecabet was potentiated. These results suggest that oral dosing of ecabet reduces the peptic activity of gastric juice by precipitating pepsin, which is facilitated by an unknown component(s) of gastric juice, and that the inactivation of pepsinogen may also contribute to the anti-peptic activity of ecabet.

show abstract

Section: Discussionmentioning

confidence: 99%

Altered Vasoconstrictor Responsiveness in Vitamin D-Induced Arteriosclerotic Rat Aortas

Ito

Nakamura

Onoda

et al. 1993

Japanese Journal of Pharmacology

View full text Add to dashboard Cite

show abstract

Section: Accepted M Manuscriptmentioning

confidence: 99%

“…Carbenoxolone, the hemisuccinate of glcyrrhetinic acid, was previously successfully used to treat patients with peptic ulceration [81]. Licorice possesses additional endocrine effects including glucocorticoid activity, antiandrogen effects, and estrogenic activity [81][82][83]. Patients consuming excessive quantities of licorice present with hypertension and hypokalaemia [83][84][85], which may be severe enough to cause myopathy and cardiac arrhythmias.…”

Section: Accepted M Manuscriptmentioning

confidence: 99%

The role of the 11β-hydroxysteroid dehydrogenase type 2 in human hypertension

Ferrari

Lovati

Frey

2000

Journal of Hypertension

View full text Add to dashboard Cite

Please cite this article as: Paolo Ferrari, The role of 11β-hydroxysteroid dehydrogenase type 2 in human hypertension, BBA -Molecular Basis of Disease (2009Disease ( ), doi:10.1016Disease ( /j.bbadis.2009 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.A C C E P T E D M A N U S C R I P T A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPTSchoner: BBADIS-09-126, Revision 1 BBA-Series Molecular Basis of Disease, special issue on Hypertension: Chapter 4, Ferrari SUMMARYCortisol and aldosterone have the same in vitro affinity for the mineralocorticoid receptor (MR), although in vivo only aldosterone acts as a physiologic agonist of the MR, despite circulating levels of cortisol in humans and corticosterone in rodents being three orders of magnitude higher than aldosterone levels. In mineralocorticoid target organs the enzyme 11ß-hydroxysteroid dehydrogenase type 2 (11ßHSD2) inactivates 11-hydroxy steroids, to their inactive keto-forms, thus protecting the nonselective MR from activation by glucocorticoids. The gene is highly expressed in all sodium-transporting epithelia, particularly in the kidney and colon, but also in human placenta and vascular wall. Mutations in the HSD11B2 gene cause a rare monogenic juvenile hypertensive syndrome called apparent mineralocorticoid excess (AME). In AME, compromised 11ßHSD2enzyme activity results in activation of the MR by cortisol, causing sodium retention, hypokalaemia, and salt-dependent hypertension. Whereas mutations or inhibition of 11ßHSD2 by licorice have been clearly shown to produce a congenital or acquired syndrome of mineralocorticoid excess, the questions remaining are the extent to which subtle abnormalities in MR/11ßHSD2 mechanisms may contribute to essential hypertension. Studies in patients with essential hypertension showed a prolonged half-life of cortisol and an increased ratio of urinary cortisol to cortisone metabolites, suggesting a deficient 11ßHSD2 activity. These abnormalities may be genetically determined, as suggested by the association of a microsatellite flanking the HSD11B2 gene with hypertension in black patients with end-stage kidney disease and with salt sensitivity of blood pressure in healthy subjects. These findings indicate that variants of the HSD11B2 gene may contribute to the enhanced blood pressure response to salt and possibly to hypertension in humans.

show abstract

“…l-> 100 dilutions of centrifuged gastric juice samples were prepared with HCI (pH 1.94-1.98). 1.0 ml samples of each dilution were assayed by the method of Anson [2], as modified by A itken et al [I], and Henman [8]. All determinations were carried out in duplicate.…”

Section: Gastric Infusate Experimentsmentioning

confidence: 99%

Gastric Effects of Cycloheximide

Fd¹

1973

Digestion

View full text Add to dashboard Cite

50 mg/kg intraperitoneal cycloheximide reduced the volume and acid concentration of gastric secretion elicited from gastric dual-ligated rats by subcutaneous administration of 1 IU insulin, or 5 mg histamine (base). Cycloheximide reduced the volume of gastric secretion of gastric dual-ligated rats stimulated by 200 μg pentagastrin (depot preparation). Pepsin concentration was unaltered. Cycloheximide did not increase the gastric back diffusion of acid from the stomach. The pentagastrin-stimulated increase in gastric specific histidine decarboxylase activity was prevented by cycloheximide. One must conclude that the synthesis of a protein other than histidine decarbo xylase is involved in the gastric secretion of acid.

show abstract

Inhibition of peptic activity by carbenoxolone and glycyrrhetinic acid

Cited by 37 publications

References 23 publications

Altered Vasoconstrictor Responsiveness in Vitamin D-Induced Arteriosclerotic Rat Aortas

Altered Vasoconstrictor Responsiveness in Vitamin D-Induced Arteriosclerotic Rat Aortas

The role of the 11β-hydroxysteroid dehydrogenase type 2 in human hypertension

Gastric Effects of Cycloheximide

Contact Info

Product

Resources

About