Chloride transport inhibition by various types of ‘loop’ diuretics in fish opercular epithelium

Eriksson, Ola; Wistrand, Per J.

doi:10.1111/j.1748-1716.1986.tb07791.x

Cited by 20 publications

(8 citation statements)

References 24 publications

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“…Dimethylation of the sulphamoyl group of bumetanide reduced the activity. This is in good accordance with data for fish opercular skin (Eriksson & Wistrand 1986). T h e same effect of dimethylation of furosemide has been seen in the rabbit T A L H (Schlatter et al 1983).…”

Section: R E S U L T Ssupporting

confidence: 90%

Inhibitory effects of chemically‐different ‘loop’ diuretics on chloride transport across the bullfrog cornea

Eriksson

Wistrand

1986

Acta Physiologica Scandinavica

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Frog (Rana catesbeiana) corneas were mounted in an Ussing chamber, modified to facilitate dissection and to avoid edge damage to the epithelial tissue during mounting and measurements. When bathed in Conway solution of pH 7.4 the corneas displayed highly stable electrical properties, with a transepithelial potential difference (PD) of 16.6 +/- 1.O mV and a short-circuit current (SCC) of 10.3 +/- 0.8 microA cm-2. The DC resistance was 2.0 +/- 0.15 k omega X cm2 (mean +/- SE, n = 45). An increase in the intracellular cyclic AMP level induced by prostaglandin E2 and by 3-isobutyl-1-methylxanthine (IBMX) resulted in an increase in SCC. Ortho-vanadate, an inhibitor of Na+-K+-ATPase, reduced SCC. The acidic loop diuretics furosemide, bumetanide and the levorotatory form of indacrinone (MK-196) reduced SCC by about 50% at concentrations of 500, 100 and 46 microM, respectively. The (-)form of MK-196 was four times more active than the (+)form. Dimethylation of the SO2NH2 group reduced the activity of bumetanide. The basic diuretics muzolimine (Bay G 2821) and MK-447, were found, similarly, to reduce SCC by about 50% at concentrations of 500 microM. In view of their 'high ceiling' type of saluretic effects in whole animals, these basic agents should therefore be classified as 'loop' diuretics. The effects of these structurally highly different 'loop' diuretics are similar in epithelia which secrete (cornea) and in those which absorb (the renal thick ascending limb of Henle's loop; TALH) chloride ions.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: R E S U L T Ssupporting

confidence: 90%

Inhibitory effects of chemically‐different ‘loop’ diuretics on chloride transport across the bullfrog cornea

Eriksson

Wistrand

1986

Acta Physiologica Scandinavica

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“…Cl -secretion by the isolated opercular membrane of killifish is sensitive to serosal bumetanide, piretanide and furosemide (EC 50 of 40, 52 and 295·µmol·l -1 , respectively) and insensitive to DIDS and thiazide type drugs, indicating an operational NKCC-type cotransporter on the basolateral membrane (Eriksson et al, 1985;Eriksson and Wistrand, 1986). Also Cl -secretion is rapidly blocked by K + -free and Na + -free salines (Marshall, 1981), consistent with NKCC mediation of Cl -transport.…”

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confidence: 63%

Hypotonic shock mediation by p38 MAPK, JNK, PKC, FAK, OSR1 and SPAK in osmosensing chloride secreting cells of killifish opercular epithelium

Marshall

Ossum

Hoffmann

2005

Journal of Experimental Biology

110

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SUMMARY Hypotonic shock rapidly inhibits Cl- secretion by chloride cells, an effect that is osmotic and not produced by NaCl-depleted isosmotic solutions, yet the mechanism for the inhibition and its recovery are not known. We exposed isolated opercular epithelia, mounted in Ussing chambers, to hypotonic shock in the presence of a variety of chemicals: a general protein kinase C (PKC) inhibitor chelerythrine, Gö6976 that selectively blocks PKCα and β subtypes, H-89 that blocks PKA, SB203580 that blocks p38 mitogen-activated protein kinase (MAPK), as well as serine/threonine protein phosphatase (PP1 and 2A) inhibitor okadaic acid, and finally tamoxifen, a blocker of volume-activated anion channels (VSOAC). Chelerythrine has no effect on hypotonic inhibition but blocked the recovery, indicating PKC involvement in stimulation. Gö6976 had little effect, suggesting that PKCα and PKCβ subtypes are not involved. H-89 did not block hypotonic inhibition but decreased the recovery, indicating PKA may be involved in the recovery and overshoot (after restoration of isotonic conditions). SB203580 significantly enhanced the decrease in current by hypotonic shock, suggesting an inhibitory role of p38 MAPK in the hypotonic inhibition. Okadaic acid increased the steady state current, slowed the hypotonic inhibition but made the decrease in current larger; also the recovery and overshoot were completely blocked. Hypotonic stress rapidly and transiently increased phosphorylated p38 MAPK (pp38) MAPK (measured by western analysis) by eightfold at 5 min, then more slowly again to sevenfold at 60 min. Hypertonic shock slowly increased p38 by sevenfold at 60 min. Phosphorylated JNK kinase was increased by 40-50% by both hypotonic and hypertonic shock and was still elevated at 30 min in hypertonic medium. By immunoblot analysis it was found that the stress protein kinase (SPAK) and oxidation stress response kinase 1 (OSR1) were present in salt and freshwater acclimated fish with higher expression in freshwater. By immunocytochemistry,SPAK, OSR1 and phosphorylated focal adhesion kinase (pFAK) were colocalized with NKCC at the basolateral membrane. The protein tyrosine kinase inhibitor genistein (100 μmol l-1) inhibited Cl- secretion that was high, increased Cl- secretion that was low and reduced immunocytochemical staining for phosphorylated FAK. We present a model for rapid control of CFTR and NKCC in chloride cells that includes: (1) activation of NKCC and CFTR via cAMP/PKA, (2) activation of NKCC by PKC, myosin light chain kinase (MLCK), p38, OSR1 and SPAK, (3) deactivation of NKCC by hypotonic cell swelling, Ca2+ and an as yet unidentified protein phosphatase and (4) involvement of protein tyrosine kinase (PTK) acting on FAK to set levels of NKCC activity.

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“…The in vitro mummichog OE bathed in symmetrical saline develops a V t of 15-30 mV, a transepithelial potential that is strongly inhibited by addition of the α-adrenergic agonist clonidine (Marshall et al, 1993) and by the loop diuretics furosemide and bumetanide (Degnan et al, 1977;Eriksson and Wistrand, 1986) and here V t might be taken as being mostly electrogenic, in that full inhibition in symmetrical saline brings the V t close to zero. In these conditions, Na + influx and efflux respond to voltage clamping (+ and −25 mV) and conform to the predicted flux ratio equation, all indicating that Na + moves through a single barrier to Na + diffusion (Degnan and Zadunaisky, 1980).…”

Section: Functional Interpretationmentioning

confidence: 99%

Paracellular pathway remodeling enhances sodium secretion by teleost fish in hypersaline environments

Cozzi

Robertson

Spieker

et al. 2015

Journal of Experimental Biology

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In vertebrate salt-secreting epithelia, Na + moves passively down an electrochemical gradient via a paracellular pathway. We assessed how this pathway is modified to allow Na + secretion in hypersaline environments. Mummichogs (Fundulus heteroclitus) acclimated to hypersaline [2× seawater (2SW), 64‰] for 30 days developed invasive projections of accessory cells with an increased area of tight junctions, detected by punctate distribution of CFTR (cystic fibrosis transmembrane conductance regulator) immunofluorescence and transmission electron miscroscopy of the opercular epithelia, which form a gill-like tissue rich in ionocytes. Distribution of CFTR was not explained by membrane raft organization, because chlorpromazine (50 μmol l ) did not affect opercular epithelia electrophysiology. Isolated opercular epithelia bathed in SW on the mucosal side had a transepithelial potential (V t ) of +40.1±0.9 mV (N=24), sufficient for passive Na + secretion (Nernst equilibrium voltage≡E Na =+24.11 mV). Opercular epithelia from fish acclimated to 2SW and bathed in 2SW had higher V t of +45.1±1.2 mV (N=24), sufficient for passive Na + secretion (E Na =+40.74 mV), but with diminished net driving force. Bumetanide block of Cl − secretion reduced V t by 45% and 29% in SW and 2SW, respectively, a decrease in the driving force for Na + extrusion. Estimates of shunt conductance from epithelial conductance (G t ) versus short-circuit current (I sc ) plots (extrapolation to zero I sc ) suggested a reduction in total epithelial shunt conductance in 2SW-acclimated fish. In contrast, the morphological elaboration of tight junctions, leading to an increase in accessory-cell-ionocyte contact points, suggests an increase in local paracellular conductance, compensating for the diminished net driving force for Na + and allowing salt secretion, even in extreme salinities.

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Chloride transport inhibition by various types of ‘loop’ diuretics in fish opercular epithelium

Cited by 20 publications

References 24 publications

Inhibitory effects of chemically‐different ‘loop’ diuretics on chloride transport across the bullfrog cornea

Inhibitory effects of chemically‐different ‘loop’ diuretics on chloride transport across the bullfrog cornea

Hypotonic shock mediation by p38 MAPK, JNK, PKC, FAK, OSR1 and SPAK in osmosensing chloride secreting cells of killifish opercular epithelium

Paracellular pathway remodeling enhances sodium secretion by teleost fish in hypersaline environments

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