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Title: Effect of cysteamine on cytosolic somatostatin binding sites in rabbit duodenal mucosa

Abstract

Administration of cysteamine in rabbits elicited a rapid depletion of both duodenal mucosa and plasma somatostatin. A significant reduction was observed within 5 min, returning toward control values by 150 min. The depletion of somatostatin was associated with an increase in the binding capacity and a decrease in the affinity of both high- and low-affinity binding sites present in cytosol of duodenal mucosa. Incubation of cytosolic fraction from control rabbits with 1 mM cysteamine did not modify somatostatin binding. Furthermore, addition of cysteamine at the time of binding assay did not affect the integrity of /sup 125/I-Tyr11-somatostatin. It is concluded that in vivo administration of cysteamine to rabbits depletes both duodenal mucosa and plasma somatostatin and leads to up-regulation of duodenal somatostatin binding sites.

Authors:
; ; ; ;
Publication Date:
Research Org.:
Universidad de Alcala de Henares, Madrid, Spain
OSTI Identifier:
6518429
Resource Type:
Journal Article
Resource Relation:
Journal Name: Exp. Mol. Pathol.; (United States); Journal Volume: 2
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; MEA; TOXICITY; SOMATOSTATIN; BIOCHEMICAL REACTION KINETICS; IODINE 125; IODINE COMPOUNDS; MUCOUS MEMBRANES; RABBITS; SMALL INTESTINE; TRACER TECHNIQUES; AMINES; ANIMALS; BETA DECAY RADIOISOTOPES; BODY; DAYS LIVING RADIOISOTOPES; DIGESTIVE SYSTEM; DRUGS; ELECTRON CAPTURE RADIOISOTOPES; GASTROINTESTINAL TRACT; HALOGEN COMPOUNDS; INTERMEDIATE MASS NUCLEI; INTESTINES; IODINE ISOTOPES; ISOTOPE APPLICATIONS; ISOTOPES; KINETICS; MAMMALS; MEMBRANES; NUCLEI; ODD-EVEN NUCLEI; ORGANIC COMPOUNDS; ORGANIC SULFUR COMPOUNDS; ORGANS; RADIOISOTOPES; RADIOPROTECTIVE SUBSTANCES; REACTION KINETICS; THIOLS; VERTEBRATES; 560151* - Radiation Effects on Animals- Man

Citation Formats

Gonzalez-Guijarro, L., Lopez-Ruiz, M.P., Bodegas, G., Prieto, J.C., and Arilla, E.. Effect of cysteamine on cytosolic somatostatin binding sites in rabbit duodenal mucosa. United States: N. p., 1987. Web. doi:10.1016/0014-4800(87)90061-X.
Gonzalez-Guijarro, L., Lopez-Ruiz, M.P., Bodegas, G., Prieto, J.C., & Arilla, E.. Effect of cysteamine on cytosolic somatostatin binding sites in rabbit duodenal mucosa. United States. doi:10.1016/0014-4800(87)90061-X.
Gonzalez-Guijarro, L., Lopez-Ruiz, M.P., Bodegas, G., Prieto, J.C., and Arilla, E.. 1987. "Effect of cysteamine on cytosolic somatostatin binding sites in rabbit duodenal mucosa". United States. doi:10.1016/0014-4800(87)90061-X.
@article{osti_6518429,
title = {Effect of cysteamine on cytosolic somatostatin binding sites in rabbit duodenal mucosa},
author = {Gonzalez-Guijarro, L. and Lopez-Ruiz, M.P. and Bodegas, G. and Prieto, J.C. and Arilla, E.},
abstractNote = {Administration of cysteamine in rabbits elicited a rapid depletion of both duodenal mucosa and plasma somatostatin. A significant reduction was observed within 5 min, returning toward control values by 150 min. The depletion of somatostatin was associated with an increase in the binding capacity and a decrease in the affinity of both high- and low-affinity binding sites present in cytosol of duodenal mucosa. Incubation of cytosolic fraction from control rabbits with 1 mM cysteamine did not modify somatostatin binding. Furthermore, addition of cysteamine at the time of binding assay did not affect the integrity of /sup 125/I-Tyr11-somatostatin. It is concluded that in vivo administration of cysteamine to rabbits depletes both duodenal mucosa and plasma somatostatin and leads to up-regulation of duodenal somatostatin binding sites.},
doi = {10.1016/0014-4800(87)90061-X},
journal = {Exp. Mol. Pathol.; (United States)},
number = ,
volume = 2,
place = {United States},
year = 1987,
month = 4
}
  • Cysteamine (CSH) and its close derivatives deplete immunoreactive somatostatin (SS) in rat organs. The effect of CSH is dose and time dependent and reversible. Structural requirements of the analogs are the presence of either -SH or -NH2 on a two- or three-carbon alkyl molecule; both radicals together increase, whereas insertion of carboxyl abolishes potency. The duodenal ulcerogenic potency of CSH derivatives is correlated significantly with their SS-depleting activity in the gastric mucosa. The mechanism of this action of CSH is poorly understood, but it is not caused by increased release, enhanced degradation of the peptide, or selective necrosis of SSmore » cells. It is likely that in the intracellular environment CSH causes a conformational change in the peptide that affects the antigenic and functional properties of SS.« less
  • To investigate the possible impairment of defensive mechanisms in cysteamine-induced duodenal ulceration, the effect of cysteamine on the neutralization of acid by the duodenum and the back-diffusion of hydrogen ions into the duodenal mucosa has been studied. The results obtained were as follows. (1) The intraduodenal pH started to decrease between 3 and 4 hr after cysteamine injection. (2) By perfusion of the duodenal loop excluding the opening of bile and pancreatic ducts, the amount of hydrogen ions (H+) neutralized was found to be significantly lower in cysteamine-treated animals than in the controls. (3) the back-diffusion of luminal H+ intomore » the duodenal mucosa, estimated by measuring the H+ disappearance from the test solution including 100 mM HCl, was significantly increased by cysteamine. From these findings, it has been concluded that cysteamine reduces the resistance of duodenal mucosa to acid coming from the stomach.« less
  • The early morphologic sequelae induced by the duodenal ulcerogen, cysteamine, have been studied in rats by transmission electron microscopy. Cysteamine was administered per os at 70 mg/100 g body wt to groups of female rats sacrificed at 30 min, 1, 2, 4, 8, 12, 20, and 24 hr after chemical treatment, and duodenal tissue sampled from the antimesenteric side of the proximal duodenum, where ulcers develop, was studied. Emphasis was placed on early times as our previous scanning electron microscopic data had demonstrated enhanced in situ cellular necrosis and surface cavitation at 2-4 hr after cysteamine treatment. Results indicated intracellularmore » changes as early as 30 min after treatment and prior to damage of the columnar cell microvilli or epithelial tight junctions. A staging of observed cellular degenerative changes suggested early apical endoplasmic reticular swelling and loss of cytoplasmic ground substance, followed later by moderate internal disruption of mitochondria. Through these stages the cell surface microvilli remained morphologically normal. Subsequently, microvilli degenerated and mitochondrial fine structure became severely disrupted and cell contents were expelled. Deeper villous changes such as separation of columnar cells from the lamina propria and alterations of selected elements within the lamina propria were observed. These data suggest that intracellular cytotoxic reactions at the villous tips occur early and may precede the influence of intraluminal damaging factors induced by cysteamine.« less
  • The authors study the effect of dalargin on ornithine decarboxylase in homogenates of the duodenal ulcer from rats with experimental duodenal ulcer induced by cysteamine. Activity of the enzyme was expressed in pmoles /sup 14/CO/sub 2//mg protein/h. Protein was determined by Lowry's method. The findings indicate that stimulation of ornithine decarboxylase and the antiulcerative effect of dalargin may be due to direct interaction of the peptide with cells of the intestinal mucosa and with enterocytes.
  • Enzymatic conversion of all-trans-{beta}-carotene to retinal by a partially purified enzyme from rabbit and rat intestinal mucosa was demonstrated. The enzymatic product was characterized based on the following evidence: (i) the product gave rise to its O-ethyloxime by treatment with O-ethylhydroxylamine with an absorption maximum at 363 nm in ethanol characteristics of authentic retinal O-ethyloxime. High-pressure liquid chromatography (HPLC) of this derivative yielded a sharp peak with a retention time of 7.99 min corresponding to the authentic compound; (ii) the mass spectrum of the O-ethyloxime of the enzymatic product was identical to that of authentic retinal O-ethyloxime; (iii) the specificmore » activity of the enzymatically formed ({sup 14}C)retinal O-ethyloxime remained constant even after repeated crystallization; (iv) the enzymatic product exhibited an absorption maximum at 370 nm in light petroleum characteristic of authentic retinal. This retinol was enzymatically esterified to retinyl palmitate by rat pancreatic esterase with a retention time of 10 min on HPLC corresponding to authentic retinyl palmitate. Thus, the enzymatic product of {beta}-carotene cleavage by the partially purified intestinal enzyme was unequivocally confirmed to be retinal.« less