Acetylcholine-induced intracellular acidosis in rabbit salivary gland acinar cells

Lau, K. R.; Elliott, A.; Brown, Peter de Nully

doi:10.1152/ajpcell.1989.256.2.c288

Cited by 64 publications

(52 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The demonstration that the mechanism which caused the acidosis is independent of the presence of Na+ eliminates the possibility that the HCO3-efflux which underlies the acidosis could be mediated by a Na+-3HCO3-co-transport mechanism similar to that described in mammalian renal epithelia (Yoshitomi, Burckhardt & Fromter, 1985;Soleimani, Grassl & Aronson, 1987). This in turn indirectly supports our previous conclusion that HCO3-efflux probably takes place through non-specific anion channels (Lau et al 1989;Brown et al 1989b). Figure 3 also shows that following the acidosis pHi recovered to the control (pre-ACh stimulation) value in acini equilibrated in control or Na+-free (Li+) medium, although recovery was significantly slower in Na+-free (Li+) medium (Table 2).…”

Section: Effect Of Na+-free Conditions On Acetylcholine-evoked Changesupporting

confidence: 90%

“…We have previously shown that muscarinic stimulation of rabbit mandibular gland acinar cells evokes an intracellular acidosis followed by a recovery of pH1 towards control levels (Lau et al 1989;Brown et al 1989 b). The acidosis appears to be the result of HCO3-efflux from the cell, while the subsequent recovery of pH, may be mediated by Na+-H+ exchange since it is amiloride sensitive (Lau et al 1989;Brown et al 1989 b).…”

Section: Effect Of Na+-free Conditions On Acetylcholine-evoked Changementioning

confidence: 91%

“…The animals were killed by an intravenous overdose of sodium pentobarbitone. The methods used for isolating the acini, loading them with the fluorescent pH-sensitive dye 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF), and measuring and calibrating the fluorescence in terms of intracellular pH (pHi) have been described previously (Lau et al 1989; Brown, Elliott & Lau, 1989b).…”

Section: Methodsmentioning

confidence: 99%

“…The acidosis appears to be the result of HCO3-efflux from the cell, while the subsequent recovery of pH, may be mediated by Na+-H+ exchange since it is amiloride sensitive (Lau et al 1989;Brown et al 1989 b). Figure 3 shows that ACh caused a marked intracellular acidosis in cells equilibrated in Na+-free media regardless of whether NMDG or Li+ was the Na+ substitute.…”

Section: Effect Of Na+-free Conditions On Acetylcholine-evoked Changementioning

confidence: 99%

“…In addition to the basolateral Na+-K+-ATPase these processes probably include a basolateral (Case, Hunter, Novak & Young, 1984;Lau, Yates & Case, 1990). Considerable evidence also exists for the presence in these cells of a Na+-H+ exchanger Pirani, Evans, Cook & Young, 1987;Steward, Seo & Case, 1989;Lau, Elliott & Brown, 1989). While the evidence for an obligatory role for the Na+-H+ exchanger in electrolyte transport in this tissue is not strong (see e.g.…”

Section: Introductionmentioning

confidence: 98%

See 4 more Smart Citations

The effects of Na+ replacement on intracellular pH and [Ca2+] in rabbit salivary gland acinar cells.

Elliott

Lau

Brown

1991

The Journal of Physiology

View full text Add to dashboard Cite

SUMMARY1. The role of Na+-dependent mechanisms in regulating the intracellular pH (pHi) and free calcium concentration ([Ca2+]i) in acinar cells of the rabbit mandibular salivary gland was examined. The fluorescent dyes BCECF and Fura-2 were used to measure pHi and [Ca2+]i respectively in suspensions of isolated acini.2. Replacement of all of the extracellular Na+ with N-methyl-D-glucamine (NMDG) decreased resting pHi from a control value of 741-7-2 to 6-8-6-9. Re-addition of Na+ or Li+ caused a recovery of pHi towards control values. This recovery was blocked by 10-50 ,uM-ethylisopropylamiloride (EIPA), suggesting that it was mediated by Na+-H+ exchange. The rate of recovery of pHi when Na+ was reintroduced increased with Na+ concentration with an apparent Km for Na+ of around 30 mM.3. Replacement of all of the extracellular Na+ with Li+ caused only a small decrease in resting pHi.4. Stimulation of acini with 1 uM-acetylcholine (ACh) evoked an intracellular acidosis both under control conditions and when acini were bathed in Na+-free media. Following the acidosis pHi recovered in acini bathed in either control medium or Na+-free (Li+) medium, but not in acini bathed in Na+-free (NMDG) medium or in control medium containing EIPA.5. Stimulation of acini bathed in Na+-free, HC03--free medium with ACh did not cause any change in pHi.6. Re-addition of Na+ to acini bathed in Na+-free, HC03--free medium evoked the same rate of alkalinization whether or not the acini had been stimulated with ACh, suggesting that receptor stimulation per se did not lead to an activation of acid extrusion.7. Resting [Ca2+]i was elevated in acini bathed in Na+-free (NMDG) medium, but not in acini bathed in Na+-free (Li+) medium.8. ACh evoked a maintained rise in [Ca2+]i in acini bathed in control medium and in Na+-free media with either NMDG or Li' as the Na+ substitute.9. Experiments in which external Ca2+ was reduced to low levels (by the addition of EGTA) just prior to addition of ACh showed that ACh released intracellular Ca2+ stores under both control and Na+-free conditions. 10. In acini bathed in Na+-free (NMDG) [Ca2+]i could also be reduced under these conditions by alkalinizing the cytosol using the weak base trimethylamine. 11. Our results suggest that Na+-H+ exchange is the major acid extrusion mechanism in isolated rabbit mandibular acinar cells. The exchanger is responsible for maintaining pHi above equilibrium, and also underlies the recovery of pH, when the cytosol is acidified by stimulation with ACh.12. Removal of external Na+ does not appear to interfere with receptor-operated Ca mobilization in rabbit mandibular acinar cells. The effects of Na+ removal and readdition on [Ca2+]i appear to be secondary to the changes in pHi, and are most easily explained by a direct interaction between Ca2+ and H+.

show abstract

Section: Effect Of Na+-free Conditions On Acetylcholine-evoked Changesupporting

confidence: 90%

Section: Effect Of Na+-free Conditions On Acetylcholine-evoked Changementioning

confidence: 91%

Section: Methodsmentioning

confidence: 99%

Section: Effect Of Na+-free Conditions On Acetylcholine-evoked Changementioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

See 3 more Smart Citations

The effects of Na+ replacement on intracellular pH and [Ca2+] in rabbit salivary gland acinar cells.

Elliott

Lau

Brown

1991

The Journal of Physiology

View full text Add to dashboard Cite

show abstract

Effects of cachexia due to cancer on whole body and skeletal muscle protein turnover

Dworzak

Ferrari²,

Gavazzi

et al. 1998

Cancer

View full text Add to dashboard Cite

Conflicting data in the literature may be accounted for by the different selection of patients and controls. Furthermore, WBP kinetics is the result of the metabolism of at least two compartments, the muscle and the nonmuscle compartments (including the tumor), which can change in opposite ways. In patients with cachexia due to cancer, the skeletal compartment appears to be the more compromised, with a significant decrease in SMP synthesis.

show abstract

Regulation of changes in cytosolic Ca2+ and Na+ concentrations in rat submandibular gland acini exposed to carbachol and ATP

Hurley¹,

Ryan²,

Moore³

1996

J. Cell. Physiol.

View full text Add to dashboard Cite

The relationship between cytosolic concentrations of Ca2+ (Ca2i) and Na+ (Na+i) were studied in preparations of rat submandibular and pancreatic acini loaded with the Ca(2+)-sensitive dye Fura-2 or the Na(+)-sensitive dye SBFI. Pancreatic acini showed no changes in Na+i during either transient or persistent changes in Ca2+i. Increases in Ca2+i produced by exposure of submandibular gland acini to carbachol, a muscarinic cholinergic agonist, were followed by an increase in Na+i after a delay of 5-10 s. When Ca2+ stores were mobilized without Ca2+ influx Na+i also increased, but in acini loaded with BAPTA, a nonfluorescent Ca2+ chelator, the transient increase in Ca2+ caused by mobilization of stored Ca2+ was virtually abolished, as was the increase in Na+i. In the presence of inomycin, increases in Ca2+i were followed by increases in Na+i. Ca(2+)-dependent increases in Na+i were abolished in Na(+)-free buffer and by the presence of furosemide, a blocker of Na(+)-K(+)-2Cl- cotransport. In other studies, extracellular ATP (ATPo) produced an increase in Ca2+i and Na+i. The steady-state increase in Ca(i)2+ was reduced by increasing extracellular Na+ concentrations (Na+o in dose-dependent fashion (IC50 = 16.4 +/- 4.7 mM Na+). Likewise, increasing Na+o reduced ATPo-stimulated 45Ca2+ uptake at steady state (IC50 = 15.8 +/- 9.2 mM Na+). Changing Na+o had no effect on carbachol-stimulated increases in Ca2+i. We conclude that, in rat submandibular gland acini, ATPo promotes an increase in Ca2+i and Na+i via a common influx pathway and that, under physiologic conditions, Na+ significantly limits the ATPo-stimulated increase in Ca2+i. In the presence of carbachol, however, Na+i rises in Ca2+i-dependent fashion in submandibular gland acini via stimulation of Na(+)-K(+)-2Cl- cotransport.

show abstract

Acetylcholine-induced intracellular acidosis in rabbit salivary gland acinar cells

Cited by 64 publications

References 1 publication

The effects of Na+ replacement on intracellular pH and [Ca2+] in rabbit salivary gland acinar cells.

The effects of Na+ replacement on intracellular pH and [Ca2+] in rabbit salivary gland acinar cells.

Effects of cachexia due to cancer on whole body and skeletal muscle protein turnover

Regulation of changes in cytosolic Ca2+ and Na+ concentrations in rat submandibular gland acini exposed to carbachol and ATP

Contact Info

Product

Resources

About