Dantrolene and basal ileal sodium and chloride transport: involvement of calcium stores

Donowitz, Mark; Cusolito, S.; Battisti, L.; Sharp, Geoffrey W. G.

doi:10.1152/ajpgi.1983.245.6.g780

Cited by 9 publications

(4 citation statements)

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“…Its kinetic properties and sensitivity to vitamin D status are consistent with the conclusion that it represents a basal-lateral membrane-localized calcium pump. On the other hand, studies of neural and hormonal regulation of NaC1 absorption [8,9] lead to the conclusion that intestinal cells, like secretory epithelial cells [e.g., 30, 33] possess intracellular compartments which actively accumulate calcium. Since both endoplasmic reticulum and Golgi membranes may participate in calcium sequestration in exocrine acinar cells [20], it will be interesting to learn whether the ATP-dependent calcium transport activity measured in isolated basal-lateral membrane samples might actually be shared between the basal-lateral membrane population and previously unsuspected Golgi-and endoplasmic reticulum-derived populations.…”

Section: Discussionmentioning

confidence: 99%

Complex subcellular distributions of enzymatic markers in intestinal epithelial cells

et al. 1985

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Current procedures for isolating intestinal epithelial cell surface and intracellular membranes are based on the assumption that each organelle is marked by some unique constituent. This assumption seemed inconsistent with the dynamic picture of subcellular organization emerging from studies of membrane turnover and recycling. Therefore, we have designed an alternative fractionation which is independent of a priori marker assignments. We subjected mucosal homogenates to a sequence of separations based on sedimentation coefficient, equilibrium density, and partitioning in aqueous polymer two-phase systems. The resulting distributions of protein and enzymatic markers define a total of 17 physically and biochemically distinct membrane populations. Among these are: basal-lateral membranes, with Na,K-ATPase enriched 21-fold; brush-border membranes, with alkaline phosphatase enriched as much as 38-fold; two populations apparently derived from the endoplasmic reticulum; a series of five populations believed to have been derived from the Golgi complex; and a series of five acid phosphatase-rich populations which we cannot identify unequivocally. Each of the five enzymatic markers we have followed is associated with a multiplicity of membrane populations. Basallateral, endoplasmic reticulum, and Golgi membranes contain alkaline phosphatase at the same specific activity as the initial homogenate. Similarly, Na,K-ATPase appears to be associated with Golgi, endoplasmic reticulum, and brush-border membranes at specific activities two- to seven-fold that of the initial homogenate.

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Section: Discussionmentioning

confidence: 99%

Complex subcellular distributions of enzymatic markers in intestinal epithelial cells

et al. 1985

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“…The stimulation of electrolyte absorption by dantrolene does not have immediate clinical implications for the therapy of diarrhoea. It is not known whether dantrolene has similar effects under in vivo conditions [2]. Moreover, as an agent that stimulates Na ÷ and C1-absorption by affecting intracellular calcium stores, dantrolene appears to have al- Table 1 Effect of dantrolene on unidirectional fluxes of Na ÷ and C1-in the small intestine of control and G. lamblia-infected animals Group/fluxes Control (U equiv, cm 2 h I) Experimental (U equiv, cm 2 h-1 ) Values are expressed as mean + SE of six determinations.…”

Section: Resultsmentioning

confidence: 99%

“…The role of intracellular calcium stores in the * Corresponding author. regulation of ion transport is probed by the use of dantrolene, a drug used clinically as a skeletal muscle relaxant that has been shown to trap calcium in intracellular stores in skeletal muscle [2]. A wide variety of hormones and neurotransmitters have been shown to cause cellular Ca 2+ mobilisation for the expression of an appropriate biological response.…”

Section: Introductionmentioning

confidence: 99%

Involvement of intracellular calcium stores in Giardia lamblia induced diarrhoea in mice

Gorowara¹

1994

FEMS Microbiology Letters

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The transmucosal fluxes of Na+ and Cl- were studied in Giardia lamblia-infected mice in the presence or absence of dantrolene (1-(5(p-nitrophenyl)furfurilidene-amino) hydantoin sodium hydrate). There was net secretion of Na+ and Cl- in infected animals, while in control animals there was net absorption of these ions. The addition of dantrolene resulted in significant net increase in absorption of Na+ and Cl- in control and experimental groups. Further, mouse intestinal epithelial cells were labelled with [32P]Pi and then treated with G. lamblia trophozoites and their excretory secretory products separately. The optimum time for inositol triphosphate formation was 15 min in control enterocytes as well as in treated enterocytes. A plateau was formed at higher concentrations. Since raised inositol triphosphate levels mobilize Ca2+ from intracellular stores and dantrolene traps Ca2+ within intracellular calcium stores, the present study thus suggests that intracellular calcium stores are involved in G. lamblia-induced diarrhoea in mice.

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“…Zimmer man et al [21] have shown a Ca2+ require ment for the effects of theophylline in the rat colon. Donowitz et al [7] have provided evi dence from studies with dantrolene that in tracellular Ca2+ stores can have a regulatoryrole in basal ion transport in the ileum. It is possible that these intracellular stores could also be involved in the secretory responses observed after addition of A23187 or the secretory detergents which possess similar ionophore activity [17,18].…”

Section: Discussionmentioning

confidence: 99%

Use of Calcium Depletion and Chlorpromazine to Study Calcium Dependence of Secretory Detergent Action in the Colon

Maenz¹,

Forsyth

1987

Digestion

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The role of Ca²⁺ in the in situ secretory response of rat colon and pig ileum was studied by chelation depletion of Ca²⁺ and by treatment with chlorpromazine. The effect of depleting lumenal Ca²⁺ by chelation and the effect of intraperitoneal administration of chlorpromazine were determined relative to colonic permeability and net fluid flux measured across the rat colon or pig ileum. (1) Replacement of Ca²⁺ in the perfusate by 1.0 mM ethyleneglycol-(bis-β-ethylaminoether) (EGTA) did not produce significant changes in the net absorptive fluid flux measured in the control state or in the net secretory fluid flux caused by secretory detergent agents. The concentration of EGTA used in the perfusate did not alter mucosal permeability. (2) Nonsecretory bile acids or A23187 had no effect on net colonic fluid flux or on colonic permeability to mannitol in the rat. The known correlation between net fluid flux and increased colonic permeability to polar molecules has been confirmed for the secretory detergent compounds. (3) Chlorpromazine pretreatment caused a partial reversal of net secretory fluid fluxes induced by deoxycholate and high concentrations (6.0 mM) of ricinolate and dioctyl sulfosuccinate without significantly altering mucosal permeability to mannitol. We conclude that depletion of lumenal Ca²⁺ is not an effective method for determining the possible Ca²⁺ dependence of these intestinal secretory events. The antisecretory actions of chlorpromazine may provide some indirect evidence for Ca²⁺ involvement in the secretory effects of the detergent class of laxative compounds. Permeability may be essential for secretion caused by these agents, but the driving force would appear to be provided by the active transfer of electrolytes from the blood to the lumen of the colon.

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Dantrolene and basal ileal sodium and chloride transport: involvement of calcium stores

Cited by 9 publications

References 0 publications

Complex subcellular distributions of enzymatic markers in intestinal epithelial cells

Complex subcellular distributions of enzymatic markers in intestinal epithelial cells

Involvement of intracellular calcium stores in Giardia lamblia induced diarrhoea in mice

Use of Calcium Depletion and Chlorpromazine to Study Calcium Dependence of Secretory Detergent Action in the Colon

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