An ammonium pulse inhibits fluid secretion

Lau, K. R.; Case, R. M.

doi:10.1007/bf02207280

Cited by 4 publications

(5 citation statements)

References 12 publications

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“…However, our experimental setup virtually rules this out, because we measured NBC activity after a NH 4 ϩ prepulse and preincubation in Na ϩ -free, DMA-containing solution. Several groups (25,31,54,57) have found strong inhibition of anion secretion after exposure to NH 4 ϩ in different secretory epithelia. In some of these studies, the inhibitory effect could be demonstrated as long as 30 min after NH 4 Cl exposure (25,54).…”

Section: Discussionmentioning

confidence: 99%

“…Several groups (25,31,54,57) have found strong inhibition of anion secretion after exposure to NH 4 ϩ in different secretory epithelia. In some of these studies, the inhibitory effect could be demonstrated as long as 30 min after NH 4 Cl exposure (25,54). To verify this for carbachol stimulation in the murine colon, we measured I sc in Ussing chambers using the murine colonic mucosa after a NH 4 Cl prepulse and DMA preincubation.…”

Section: Discussionmentioning

confidence: 99%

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Carbachol increases Na⁺-HCO₃⁻ cotransport activity in murine colonic crypts in a M₃⁻, Ca²⁺/calmodulin-, and PKC-dependent manner

Bachmann

Reichelt²,

Tuo³

et al. 2006

American Journal of Physiology-Gastrointestinal and Liver Physi

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The Na(+)-HCO(3)(-) cotransporter (NBC) mediates HCO(3)(-) import into the colonocyte via its pNBC1 isoform. Whereas renal kNBC1 is inhibited by increased cAMP levels, pNBC1 is stimulated. Cholinergic stimulation activates renal NBC, but the effect on intestinal NBC is unknown. Therefore, crypts were isolated from the murine proximal colon by Ca(2+) chelation and loaded with the pH-sensitive dye 2',7'-bis-carboxyethyl-5,6-carboxyfluorescein. Na(+)-HCO(3)(-) cotransport activity was calculated from the dimethylamiloride-insensitive (500 microM) intracellular pH recovery from an acid load in the presence of CO(2)-HCO(3)(-) and the intracellular buffering capacity. Carbachol strongly increased Na(+)-HCO(3)(-) cotransport activity compared with control rates. Ca(2+) chelation with BAPTA-AM, blockade of the M(3) subtype of muscarinergic receptors with 4-diphenylacetoxy-N-methylpiperidine methiodide, and inhibition of Ca(2+)/calmodulin kinase II with KN-62 all caused significant inhibition of the carbachol-induced NBC activity increase. Furthermore, PKC inhibition with Gö-6976 and Gö-6850 significantly reduced the carbachol effect, which may be related to the unique NH(2)-terminal consensus site for PKC-dependent phosphorylation of pNBC1. We conclude that NBC in the murine colon is thus activated by carbachol, consistent with its presumed function as an anion uptake pathway during intestinal anion secretion, but that the signal transductions pathways are distinct from those involved in the cholinergic activation of renal NBC1.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Carbachol increases Na⁺-HCO₃⁻ cotransport activity in murine colonic crypts in a M₃⁻, Ca²⁺/calmodulin-, and PKC-dependent manner

Bachmann

Reichelt²,

Tuo³

et al. 2006

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…In perfused rabbit mandibular glands, the weak base NH 4 Cl had dramatic inhibitory effects upon ACh‐evoked fluid secretion (Lau, Donohue & Case, 1996). Even at concentrations as low as 0.5 mM, NH 4 Cl totally inhibited fluid secretion.…”

Section: Discussionmentioning

confidence: 99%

“…It therefore seems unlikely that enhancement of agonist-evoked intracellular Ca¥ release by acetate could fully explain the prolonged elevation in secretion in rabbit mandibular glands. In perfused rabbit mandibular glands, the weak base NHÚCl had dramatic inhibitory effects upon ACh-evoked fluid secretion (Lau, Donohue & Case, 1996). Even at concentrations as low as 0•5 mÒ, NHÚCl totally inhibited fluid secretion.…”

Section: Fluid Secretionmentioning

confidence: 93%

Modulation of calcium signals by intracellular pH in isolated rat pancreatic acinar cells

Speake

Elliott

1998

The Journal of Physiology

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We have investigated the interactions between intracellular pH (pHi) and the intracellular free calcium concentration ([Ca2+]i) in isolated rat pancreatic acinar cells. The fluorescent dyes fura‐2 and BCECF were used to measure [Ca2+]i and pHi, respectively. Sodium acetate and ammonium chloride (NH4Cl) were used to acidify and alkalinize pHi, respectively. Cytosolic acidification had no effect on [Ca2+]i in resting pancreatic acinar cells, whereas cytosolic alkalinization released Ca2+ from intracellular stores. Cytosolic acidification using either acetate or a CO2‐HCO3−‐buffered medium enhanced Ca2+ signals evoked by acetylcholine (ACh) and cholecystokinin (CCK). In contrast, both NH4Cl and trimethylamine (TMA) inhibited Ca2+ signals during stimulation with either ACh or CCK. This inhibitory effect was also observed in the absence of extracellular Ca2+, and was therefore not due to changes in Ca2+ entry. Calcium oscillations evoked by physiological concentrations of CCK were enhanced by cytosolic acidification and inhibited by cytosolic alkalinization. In order to determine the effects of pHi upon Ca2+ handling by intracellular Ca2+ stores, intraorganellar [Ca2+] was monitored using the low affinity Ca2+ indicator mag‐fura‐2 in permeabilized cells. Addition of NH4Cl, which is expected to alkalinize intraorganellar pH, did not alter intraorganellar [Ca2+] in permeabilized cells, suggesting that changing intraorganellar pH does not release Ca2+ from intracellular stores. Addition of NH4Cl or acetate also did not affect the rate of Ca2+ release induced by inositol 1,4,5‐trisphosphate (InsP3). Modification of extraorganellar (‘cytosolic’) pH did not affect the rate of ATP‐dependent Ca2+ uptake into stores, but did modify the rate of Ca2+ release evoked by submaximal concentrations of InsP3. The rate of Ca2+ release was increased at more alkaline extraorganellar pHs. These results would suggest that manipulation of intraorganellar pH does not affect Ca2+ handling by the intracellular stores. In contrast, extraorganellar (‘cytosolic’) pH does affect InsP3‐induced Ca2+ release from the stores. In conclusion, changes in intracellular pH in pancreatic acinar cells can profoundly alter cytosolic [Ca2+]. This may shed light on earlier observations whereby cell‐permeant weak acids and bases can modulate fluid secretion in epithelia.

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“…Unfortunately, it is difficult to distinguish these two possibilities experimentally, and the evidence in the present study is broadly consistent with either hypothesis. Relevance to acinar cell electrolyte secretion Weak acids and bases have been reported to alter the rate of fluid and electrolyte transport in a diverse range of epithelia exocrine glands weak acids have been reported to stimulate salivary fluid secretion (Novak & Young 1989), while NH4Cl has dramatic inhibitory effects, even at the very low concentration of 0 5 mm (Lau, Donohue & Case, 1996). Furthermore, as discussed above, weak bases have been found to alter both the rate of tracer ion fluxes (Seagrave et al 1992a, b) and the activity of membrane ion channels (Hayashi et al 1992; in acinar cells.…”

Section: Ca2+ Entrymentioning

confidence: 99%

Intracellular alkalinization mobilizes calcium from agonist‐sensitive pools in rat lacrimal acinar cells.

Yodozawa

Speake

Elliott

1997

The Journal of Physiology

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1. We have investigated interactions between intracellular pH (pHJ) and the intracellular free calcium concentration ([Ca2+]i) in collagenase-isolated rat lacrimal acinar cells. The fluorescent dyes fura-2 and 2',7'-bis(carboxyethyl)-5-carboxyfluorescein (BCECF) were used to measure [Ca2+] Ca2+ from the intracellular agonist-sensitive Ca2+ pool. However, releasing stored Ca2+ via alkalinization does not appear to trigger significant Ca2+ entry, perhaps because intracellular alkalinization inhibits either the Ca2P entry pathway or the mechanism which couples the entry pathway to store depletion.The primary signal controlling fluid and electrolyte Nae and with changes in intracellular pH (see Nauntofte, secretion in exocrine acinar cells is an increase in the intra-1992, for review). The interactions between these changes in cellular free calcium concentration ([Ca2P]

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An ammonium pulse inhibits fluid secretion

Cited by 4 publications

References 12 publications

Carbachol increases Na⁺-HCO₃⁻ cotransport activity in murine colonic crypts in a M₃⁻, Ca²⁺/calmodulin-, and PKC-dependent manner

Carbachol increases Na⁺-HCO₃⁻ cotransport activity in murine colonic crypts in a M₃⁻, Ca²⁺/calmodulin-, and PKC-dependent manner

Modulation of calcium signals by intracellular pH in isolated rat pancreatic acinar cells

Intracellular alkalinization mobilizes calcium from agonist‐sensitive pools in rat lacrimal acinar cells.

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An ammonium pulse inhibits fluid secretion

Cited by 4 publications

References 12 publications

Carbachol increases Na+-HCO3− cotransport activity in murine colonic crypts in a M3−, Ca2+/calmodulin-, and PKC-dependent manner

Carbachol increases Na+-HCO3− cotransport activity in murine colonic crypts in a M3−, Ca2+/calmodulin-, and PKC-dependent manner

Modulation of calcium signals by intracellular pH in isolated rat pancreatic acinar cells

Intracellular alkalinization mobilizes calcium from agonist‐sensitive pools in rat lacrimal acinar cells.

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Carbachol increases Na⁺-HCO₃⁻ cotransport activity in murine colonic crypts in a M₃⁻, Ca²⁺/calmodulin-, and PKC-dependent manner

Carbachol increases Na⁺-HCO₃⁻ cotransport activity in murine colonic crypts in a M₃⁻, Ca²⁺/calmodulin-, and PKC-dependent manner