Forskolin mimics the hydrosmotic action of vasopressin in the urinary bladder of toads Bufo marinus.

Sousa, R. C. de; Grosso, A.

doi:10.1113/jphysiol.1985.sp015774

Cited by 11 publications

(1 citation statement)

References 30 publications

(30 reference statements)

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“…These increases in cAMP levels activate protein kinase A (PKA), leading to the translocation and insertion of active AQP2 channels into the apical membrane (13,14). Other agents that increase the levels of intracellular cAMP (e.g., forskolin and calcitonin) and Tables 1 and 2, respectively. cAMP analogues (e.g., 8-Br-cAMP) stimulate PKA, AQP2 phosphorylation and membrane expression, and free water uptake (24)(25)(26)(27)(28)(29). Protein kinase A blockade inhibits vasopressin-mediated AQP2 membrane expression and free water uptake (30)(31)(32)(33).…”

Section: Discussionmentioning

confidence: 99%

Bacillus anthracis Edema Toxin Increases Fractional Free Water and Sodium Reabsorption in an Isolated Perfused Rat Kidney Model

et al. 2017

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Bacillus anthracis edema toxin (ET) consists of protective antigen (PA), necessary for host cell toxin uptake, and edema factor (EF), the toxic moiety which increases host cell cyclic AMP (cAMP). Since vasopressin stimulates renal water and sodium reabsorption via increased tubular cell cAMP levels, we hypothesized the ET would also do so. To test this hypothesis, we employed an isolated perfused rat kidney model. Kidneys were isolated and perfused with modified Krebs-Henseleit buffer. Perfusate and urine samples were obtained at baseline and every 10 min over 150 min following the addition of challenges with or without treatments to the perfusate. In kidneys perfused under constant flow or constant pressure, compared to PA challenge (n ϭ 14 or 15 kidneys, respectively), ET (13 or 15 kidneys, respectively) progressively increased urine cAMP levels, water and sodium reabsorption, and urine osmolality and decreased urine output (P Յ 0.04, except for sodium reabsorption under constant pressure [P ϭ 0.17]). In ET-challenged kidneys, compared to placebo treatment, adefovir, an EF inhibitor, decreased urine cAMP levels, water and sodium reabsorption, and urine osmolality and increased urine output, while raxibacumab, a PA-directed monoclonal antibody (MAb), decreased urine cAMP levels, free water reabsorption, and urine osmolality and increased urine output (P Յ 0.03 except for urine output with raxibacumab [P ϭ 0.17]). Upon immunohistochemistry, aquaporin 2 was concentrated along the apical membrane of tubular cells with ET but not PA, and urine aquaporin 2 levels were higher with ET (5.52 Ϯ 1.06 ng/ml versus 1.51 Ϯ 0.44 ng/ml [means Ϯ standard errors of the means {SEM}; P ϭ 0.0001). Edema toxin has renal effects that could contribute to extravascular fluid collection characterizing anthrax infection clinically.KEYWORDS anthrax, edema toxin, kidney, water reabsorption B acillus anthracis infection is characterized clinically by the marked retention and extravasation of fluid, which can compromise cardiopulmonary function and impair host defense and tissue repair (1-6). Although the loss of vascular integrity and lymphatic obstruction contribute to this fluid accumulation, the significant hyponatremia in patients in the 2001 U.S. inhalational and 2009 UK soft tissue outbreaks suggests that alterations in renal water and sodium handling may also contribute (3, 5, 7). Notably, of the two toxins produced by B. anthracis, edema toxin (ET) but not lethal toxin (LT) infusion reduced serum sodium levels in canines (8). While ET is known to produce localized edema when injected subcutaneously, understanding whether it alters renal water and sodium handling has important therapeutic implications for the fluid management of patients with severe B. anthracis infection.Edema toxin consists of protective antigen (PA), the component necessary for host cell uptake of edema factor (EF), the toxic moiety (9, 10). Edema factor has calmodulin-

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Section: Discussionmentioning

confidence: 99%

Bacillus anthracis Edema Toxin Increases Fractional Free Water and Sodium Reabsorption in an Isolated Perfused Rat Kidney Model

et al. 2017

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Water Transport across ADH-Sensitive Epithelia

Reuss

Cotton

1989

Contemporary Nephrology

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Amiloride inhibits the vasopressin-induced increase in epithelial water permeability

1990

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The vasopressin (VP)-induced increase in water permeability in high-resistance, amphibian epithelia is not altered by the abolition of net Na+ flux caused by amiloride added to the apical bathing medium. In this work we looked at the effects on water transport of amiloride added to the serosal medium at a concentration (10(-3) M) known to inhibit Na+/H+ exchange. In urinary bladders of Bufo marinus, amiloride partially blocked the hydrosmotic response to VP. A similar inhibition was found with cyclic adenosine 5'-monophosphate (cAMP) or serosal hypertonicity. We hypothesized that this effect of amiloride could be due to an inhibition of Na+/H+ and/or Na+/Ca2+ antiporters present in the epithelial basolateral membrane and looked at the effects of the diuretic in Na(+)-free media. A similar degree of inhibition of water flow was still found, thus showing that amiloride acts on a cell target other than the antiporters. In toad skin, amiloride did not inhibit the hydrosmotic response to VP and to isoproterenol; however the response to high K+ was significantly reduced. Among the amiloride cell targets described so far, adenylate cyclase and protein kinase A appear to be the best candidates to explain the inhibition of the hydrosmotic response reported here. Direct measurements of intracellular cAMP are needed however to substantiate this hypothesis.

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Forskolin mimics the hydrosmotic action of vasopressin in the urinary bladder of toads Bufo marinus.

Cited by 11 publications

References 30 publications

Bacillus anthracis Edema Toxin Increases Fractional Free Water and Sodium Reabsorption in an Isolated Perfused Rat Kidney Model

Bacillus anthracis Edema Toxin Increases Fractional Free Water and Sodium Reabsorption in an Isolated Perfused Rat Kidney Model

Water Transport across ADH-Sensitive Epithelia

Amiloride inhibits the vasopressin-induced increase in epithelial water permeability

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