The Mechanisms of Fluoride Uptake by the Brush-Border Membrane Vesicles (BBMV) of Rabbit Small Intestine and Kidney

Hdl Handle:
http://hdl.handle.net/10675.2/346132
Title:
The Mechanisms of Fluoride Uptake by the Brush-Border Membrane Vesicles (BBMV) of Rabbit Small Intestine and Kidney
Authors:
He, Han
Abstract:
Ingested fluoride is absorbed rapidly from the gastrointestinal tract The literature indicates the following about the gastrointestinal absorption of fluoride: 1. the rate and extent of absorption are reduced by certain divalent and trivalent cations; 2 . the rate of absorption from the intact stomach is dependent on the magnitude of the transmucosal pH gradient; 3. the rate of absorption from the intact small intestine is not affected significantly by the pH of the bulk solution; 4. there is evidence that some unidentified, energy-requiring mechanism(s) may be involved in the intestinal absorption of fluoride; 5. although DIDS (4,4'-diisothiocyanostilbene-2,2'-disulfonate) has little or no effect on fluoride movement across the human red blood cell membrane or the cortical collecting duct of the rabbit, it partially inhibits uptake by rat submandibular salivary cells. This study was carried out to test the hypothesis that the intestinal and renal absorption of fluoride occurs by more than one mechanism. That is, some fluoride is absorbed in a pH-dependent manner by HF diffusion through the apical membrane of intestinal cells, possibly via aquaporins. The bulk of fluoride, however, is absorbed as ionic fluoride via other routes possibly including passage through intercellular gap junctions, aquaporins, F'-C1‘ and/or F'-HCCV exchangers), conductive pathway and specific anion-transporting protein carriers. The specific aims of this study were to determine the effects of pH, pH gradients, sodium, potassium, chloride and bicarbonate gradients, DIDS ( a specific inhibitor of anion transport), bis-( 13-di butyl barbituric acid) pentamethine oxonol (diBAC, another specific inhibitor of anion transport), diethylpyrocarbonate (DEP, a histidine-specific reactive reagent), parachloromercuri-benzene sulfonate (PCMBS, a sulfhydryl-modifying reagent which is an inhibitor of aquaporins), and valinomycin on the movement of fluoride across brush border membrane vesicles (BBMV) prepared from the proximal intestinal mucosa and renal cortex of the rabbit The effect of pH gradients on fluoride transfer in everted intestinal sacs from the rat was also studied To accomplish the goals stated, two models were used: (1) the "everted sac" technique using tissue from rats; and (2) BBMV prepared from intestinal mucosal scrapings and renal cortex of rabbits. Both methods allow control of the compositions of the solutions on both surfaces. The everted sac technique involves the full thickness of the intestinal wall whereas BBMV involve only cell membranes from the luminal aspect of the mucosal cells (mainly enterocyte and some Goblet cells, enteroendocrine cells, Paneth cells, etc.). A comparison of the findings using these two approaches may show that the variables to be tested have different effects depending on the model and thus reveal the existence of different absorptive mechanisms or pathways. The variables to be tested included: (1) pH; (2) pH gradients; (3) specific inhibitors of (a) anion transport (DIDS and diBAC, which combine with the anion transporter to form a stable derivative to inhibit anion transport) and (b) proton transport (DEP, a histidinespecific reactive reagent which has been used to characterize proton and proton-coupled transport); (4) PCMBS, a sulfhydryl-modifying reagent which is a non-specific inhibitor of several transport systems including aquaporins; (5) valinomycin; and (6 ) gradients of sodium and potassium. The mechanism(s) involved in the absorption of fluoride from the intestinal tract remain poorly defined. The literature indicates that the rate of fluoride transport or migration across several types of epithelia and cell membranes is directly proportional to the magnitude of the pH gradient This dependency, however, appears not to apply to the intestinal epithelium. The present studies were designed to clarify this matter and thus contribute to an improved understanding of the basic mechanisms and pathways involved in the transport of fluoride in biological systems. The findings may have implications for the transport of other anions as well.
Affiliation:
Department of Oral Biology
Issue Date:
Jun-1997
URI:
http://hdl.handle.net/10675.2/346132
Additional Links:
http://ezproxy.gru.edu/login?url=http://search.proquest.com/docview/304382357?accountid=12365
Type:
Dissertation
Appears in Collections:
Theses and Dissertations

Full metadata record

DC FieldValue Language
dc.contributor.authorHe, Hanen
dc.date.accessioned2015-03-03T22:55:33Zen
dc.date.available2015-03-03T22:55:33Zen
dc.date.issued1997-06en
dc.identifier.urihttp://hdl.handle.net/10675.2/346132en
dc.description.abstractIngested fluoride is absorbed rapidly from the gastrointestinal tract The literature indicates the following about the gastrointestinal absorption of fluoride: 1. the rate and extent of absorption are reduced by certain divalent and trivalent cations; 2 . the rate of absorption from the intact stomach is dependent on the magnitude of the transmucosal pH gradient; 3. the rate of absorption from the intact small intestine is not affected significantly by the pH of the bulk solution; 4. there is evidence that some unidentified, energy-requiring mechanism(s) may be involved in the intestinal absorption of fluoride; 5. although DIDS (4,4'-diisothiocyanostilbene-2,2'-disulfonate) has little or no effect on fluoride movement across the human red blood cell membrane or the cortical collecting duct of the rabbit, it partially inhibits uptake by rat submandibular salivary cells. This study was carried out to test the hypothesis that the intestinal and renal absorption of fluoride occurs by more than one mechanism. That is, some fluoride is absorbed in a pH-dependent manner by HF diffusion through the apical membrane of intestinal cells, possibly via aquaporins. The bulk of fluoride, however, is absorbed as ionic fluoride via other routes possibly including passage through intercellular gap junctions, aquaporins, F'-C1‘ and/or F'-HCCV exchangers), conductive pathway and specific anion-transporting protein carriers. The specific aims of this study were to determine the effects of pH, pH gradients, sodium, potassium, chloride and bicarbonate gradients, DIDS ( a specific inhibitor of anion transport), bis-( 13-di butyl barbituric acid) pentamethine oxonol (diBAC, another specific inhibitor of anion transport), diethylpyrocarbonate (DEP, a histidine-specific reactive reagent), parachloromercuri-benzene sulfonate (PCMBS, a sulfhydryl-modifying reagent which is an inhibitor of aquaporins), and valinomycin on the movement of fluoride across brush border membrane vesicles (BBMV) prepared from the proximal intestinal mucosa and renal cortex of the rabbit The effect of pH gradients on fluoride transfer in everted intestinal sacs from the rat was also studied To accomplish the goals stated, two models were used: (1) the "everted sac" technique using tissue from rats; and (2) BBMV prepared from intestinal mucosal scrapings and renal cortex of rabbits. Both methods allow control of the compositions of the solutions on both surfaces. The everted sac technique involves the full thickness of the intestinal wall whereas BBMV involve only cell membranes from the luminal aspect of the mucosal cells (mainly enterocyte and some Goblet cells, enteroendocrine cells, Paneth cells, etc.). A comparison of the findings using these two approaches may show that the variables to be tested have different effects depending on the model and thus reveal the existence of different absorptive mechanisms or pathways. The variables to be tested included: (1) pH; (2) pH gradients; (3) specific inhibitors of (a) anion transport (DIDS and diBAC, which combine with the anion transporter to form a stable derivative to inhibit anion transport) and (b) proton transport (DEP, a histidinespecific reactive reagent which has been used to characterize proton and proton-coupled transport); (4) PCMBS, a sulfhydryl-modifying reagent which is a non-specific inhibitor of several transport systems including aquaporins; (5) valinomycin; and (6 ) gradients of sodium and potassium. The mechanism(s) involved in the absorption of fluoride from the intestinal tract remain poorly defined. The literature indicates that the rate of fluoride transport or migration across several types of epithelia and cell membranes is directly proportional to the magnitude of the pH gradient This dependency, however, appears not to apply to the intestinal epithelium. The present studies were designed to clarify this matter and thus contribute to an improved understanding of the basic mechanisms and pathways involved in the transport of fluoride in biological systems. The findings may have implications for the transport of other anions as well.en
dc.relation.urlhttp://ezproxy.gru.edu/login?url=http://search.proquest.com/docview/304382357?accountid=12365en
dc.rightsCopyright protected. Unauthorized reproduction or use beyond the exceptions granted by the Fair Use clause of U.S. Copyright law may violate federal law.en
dc.subjectFluorideen
dc.subjectIntestinal Absorptionen
dc.subjectRenal Absorptionen
dc.titleThe Mechanisms of Fluoride Uptake by the Brush-Border Membrane Vesicles (BBMV) of Rabbit Small Intestine and Kidneyen
dc.typeDissertationen
dc.contributor.departmentDepartment of Oral Biologyen
dc.description.advisorWhitford, Gary Men
dc.description.committeeBorke, James L.; Pashley, David H.; Leibach, Frederick H.en
dc.description.degreeDoctor of Philosophy (Ph.D.)en
All Items in Scholarly Commons are protected by copyright, with all rights reserved, unless otherwise indicated.