Mobilization of Ca2+ influx, but not of stored Ca2+, by extracellular ATP in rat submandibular gland acini

Hurley, Thomas W.; Ryan, M. P.; Shoemaker, Drew D.

doi:10.1016/0003-9969(94)90046-9

Cited by 22 publications

(25 citation statements)

References 14 publications

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“…Much of the work with P 2 agonists has been done with airway and nasal epithelia due to the potential implication of the findings to cystic fibrosis. Although expression of P 2 receptors in parotid and SMG acinar cells has been known for quite some time (17)(18)(19)(20)(21)(22), the mechanism by which these receptors may regulate secretion is not known. The presence and action of P 2 receptors in duct cells is known to only a very limited extent (32).…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies reported that ATP increases [Ca 2ϩ ] i in SMG acinar (22) and duct cells (32). To evaluate the contribution of the Ca 2ϩ -activated Cl Ϫ channels to the current activated by ATP we tested the effect of extracellular Ca 2ϩ and intracellular EGTA on the current.…”

Section: Measurements Of [Clmentioning

confidence: 99%

“…Agonists acting through cAMP elevation can activate CFTR in acinar and duct cells (9,16). Salivary acinar and duct cells also respond to purinergic stimulation by a change in [Ca 2ϩ ] i (17)(18)(19)(20)(21)(22). However, the identities of the receptors and whether they regulate Cl Ϫ channels in salivary gland cells are not known.…”

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Membrane-specific Regulation of Cl− Channels by Purinergic Receptors in Rat Submandibular Gland Acinar and Duct Cells

Zeng

Lee

Muallem

1997

Journal of Biological Chemistry

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Measurement of [Cl] i , BzATP in both SMG cell types largely activated the Ca 2؉ -independent, glibenclamide-sensitive Cl ؊ current, whereas UTP activated only the Ca 2؉ -dependent Cl ؊ current. We interpret this to suggest that BzATP and UTP largely activate Cl ؊ channels residing in the membrane expressing the receptor for the active nucleotide. The present studies reveal a potentially new mechanism for transcellular Cl ؊ transport in a CFTR-expressing tissue, the SMG. Coordinated action of the P 2 z (luminal) and P 2 u (basolateral) receptors can mediate part of the transcellular Cl ؊ transport by acinar and duct cells to determine the final electrolyte composition of salivary fluid.

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Section: Discussionmentioning

confidence: 99%

Section: Measurements Of [Clmentioning

confidence: 99%

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Membrane-specific Regulation of Cl− Channels by Purinergic Receptors in Rat Submandibular Gland Acinar and Duct Cells

Zeng

Lee

Muallem

1997

Journal of Biological Chemistry

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“…In the duct the same agonists reduce the transepithelial potential and Na ϩ reabsorption (6 -8). Work on the cellular level showed that cholinergic and ␣-adrenergic agonists act on salivary acinar and duct cells to increase [Ca 2ϩ ] i (10 -15), and ␤-adrenergic agonists increase cAMP (11,16).Salivary acinar and duct cells also respond to purinergic stimulation by a change in [Ca 2ϩ ] i (15,(17)(18)(19)(20)(21)(22). However, the identity of the receptors and their membrane localization is not clear.…”

mentioning

confidence: 99%

“…Salivary acinar and duct cells also respond to purinergic stimulation by a change in [Ca 2ϩ ] i (15,(17)(18)(19)(20)(21)(22). However, the identity of the receptors and their membrane localization is not clear.…”

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Characterization and Localization of P2 Receptors in Rat Submandibular Gland Acinar and Duct Cells

Lee

Zeng

Muallem

1997

Journal of Biological Chemistry

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[Ca 2؉] i and the Cl ؊ current were measured in isolated submandibular gland acinar and duct cells to characterize and localize the purinergic receptors expressed in these cells. In both cell types 2-3-benzoylbenzoyl (Bz)-ATP and ATP increased [Ca 2؉ ] i mainly by activation of Ca 2؉ influx. UTP had only minimal effect on [Ca 2؉ ] i at concentrations between 0.1 and 1 mM. However, a whole cell current recording showed that all nucleotides effectively activated Cl ؊ currents. Inhibition of signal transduction through G proteins by guanyl-5-␤-thiophosphate revealed that the effect of ATP on Cl ؊ current was mediated in part by activation of a G protein-coupled and in part by a G protein-independent receptor. BzATP activated exclusively the G protein-independent portion, whereas UTP activated only the G protein- Ϫ . Acinar cells secrete the primary, NaCl-rich fluid into the duct, which reabsorbs most of the NaCl in exchange for K ϩ -HCO 3 Ϫ (1). As in any other CFTR-expressing tissues (2-4) and Na ϩ -transporting epithelia (5), Cl Ϫ channels play a central role in transcellular ion transport in the two cell types of SMG (1). However, unlike that of other epithelia, little is known of the regulation of Cl Ϫ channels in salivary gland cells, in particular regulation by purinergic (P 2 ) receptors.In the intact salivary gland secretion is regulated by several agonists, which include cholinergic, ␣-adrenergic, and ␤-adrenergic agonists (6 -8). The agonists act on both acinar and duct cells but modulate different activities in the two cell types. In acinar cells the agonists stimulate secretion primarily by stimulation of the basolateral NaKCl 2 cotransporter (9). In the duct the same agonists reduce the transepithelial potential and Na ϩ reabsorption (6 -8). Work on the cellular level showed that cholinergic and ␣-adrenergic agonists act on salivary acinar and duct cells to increase [Ca 2ϩ ] i (10 -15), and ␤-adrenergic agonists increase cAMP (11,16).Salivary acinar and duct cells also respond to purinergic stimulation by a change in [Ca 2ϩ ] i (15,(17)(18)(19)(20)(21)(22). However, the identity of the receptors and their membrane localization is not clear. Response of duct cells to BzATP and several other nucleotides suggested that duct cells express P 2 z and P 2 Y 1 receptors (37). Response of acinar cells to BzATP was interpreted to suggest that acinar cells express P 2 z receptors (20, 22). More recently it was shown that acinar and duct cells in long term culture up-regulate the P 2 Y 2 receptors (23). However, whether native and freshly isolated cells express P 2 Y 2 receptors and how these and other purinergic receptors regulate cellular activity is not known. P 2 receptors are believed to play a central role in regulating Cl Ϫ transport in CFTR-expressing tissues (3, 4, 24 -27). Because of our recent findings of CFTR expression in SMG duct and acinar cells (28) and the expression of P 2 receptors in SMG cells (15,(17)(18)(19)(20)(21)(22), in the present work we studied the regulation of Cl Ϫ channel...

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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.

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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.

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Mobilization of Ca2+ influx, but not of stored Ca2+, by extracellular ATP in rat submandibular gland acini

Cited by 22 publications

References 14 publications

Membrane-specific Regulation of Cl− Channels by Purinergic Receptors in Rat Submandibular Gland Acinar and Duct Cells

Membrane-specific Regulation of Cl− Channels by Purinergic Receptors in Rat Submandibular Gland Acinar and Duct Cells

Characterization and Localization of P2 Receptors in Rat Submandibular Gland Acinar and Duct Cells

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

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