Document Detail

Cadmium inhibits acid secretion in stimulated frog gastric mucosa.
MedLine Citation:
PMID:  20307561     Owner:  NLM     Status:  MEDLINE    
Cadmium, a toxic environmental pollutant, affects the function of different organs such as lungs, liver and kidney. Less is known about its toxic effects on the gastric mucosa. The aim of this study was to investigate the mechanisms by which cadmium impacts on the physiology of gastric mucosa. To this end, intact amphibian mucosae were mounted in Ussing chambers and the rate of acid secretion, short circuit current (I(sc)), transepithelial potential (V(t)) and resistance (R(t)) were recorded in the continuous presence of cadmium. Addition of cadmium (20 microM to 1mM) on the serosal but not luminal side of the mucosae resulted in inhibition of acid secretion and increase in NPPB-sensitive, chloride-dependent short circuit current. Remarkably, cadmium exerted its effects only on histamine-stimulated tissues. Experiments with TPEN, a cell-permeant chelator for heavy metals, showed that cadmium acts from the intracellular side of the acid secreting cells. Furthermore, cadmium-induced inhibition of acid secretion and increase in I(sc) cannot be explained by an action on: 1) H(2) histamine receptor, 2) Ca(2+) signalling 3) adenylyl cyclase or 4) carbonic anhydrase. Conversely, cadmium was ineffective in the presence of the H(+)/K(+)-ATPase blocker omeprazole suggesting that the two compounds likely act on the same target. Our findings suggest that cadmium affects the functionality of histamine-stimulated gastric mucosa by inhibiting the H(+)/K(+)-ATPase from the intracellular side. These data shed new light on the toxic effect of this dangerous environmental pollutant and may result in new avenues for therapeutic intervention in acute and chronic intoxication.
Andrea Gerbino; Lucantonio Debellis; Rosa Caroppo; Silvana Curci; Matilde Colella
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-03-20
Journal Detail:
Title:  Toxicology and applied pharmacology     Volume:  245     ISSN:  1096-0333     ISO Abbreviation:  Toxicol. Appl. Pharmacol.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-17     Completed Date:  2010-06-11     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0416575     Medline TA:  Toxicol Appl Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  264-71     Citation Subset:  IM    
Copyright Information:
(c) 2010 Elsevier Inc. All rights reserved.
Department of General and Environmental Physiology, University of Bari, 70126 Bari, Italy.
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MeSH Terms
Adenylate Cyclase / metabolism
Cadmium / toxicity*
Carbonic Anhydrases / metabolism
Chelating Agents / pharmacology
Dose-Response Relationship, Drug
Environmental Pollutants / toxicity*
Ethylenediamines / pharmacology
Gastric Acid / secretion*
Gastric Mucosa / drug effects*,  secretion
H(+)-K(+)-Exchanging ATPase / antagonists & inhibitors
Histamine / pharmacology
Omeprazole / pharmacology
Rana esculenta
Reg. No./Substance:
0/Chelating Agents; 0/Environmental Pollutants; 0/Ethylenediamines; 16858-02-9/N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine; 51-45-6/Histamine; 73590-58-6/Omeprazole; 7440-43-9/Cadmium; EC ATPase; EC Anhydrases; EC Cyclase

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