Cholinergic receptors regulate a voltage‐insensitive but Na<sup>+</sup>‐dependent calcium influx pathway in salivary acinar cells

Morris, Andrew P.; Fuller, Catherine M.; Gallacher, D V

doi:10.1016/0014-5793(87)81435-7

Cited by 34 publications

(11 citation statements)

References 14 publications

(1 reference statement)

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“…Recently, it was reported that activation of the Na+/H + exchanger by agonists (which increase intracellular Na--and reduce intracellular H + concentrations) was followed by an increase in [Ca2+]i (Grinstein & Goetz, 1985;Siffert & Akkerman, 1987). In addition, removal of extracellular Na § eliminated the sustained phase of the increase in [Ca2+]/induced by acetylcholine stimulation of salivary acinar cells (Morris, Fuller & Gallacher, 1987). However, the increase in [Ca2+]i following the stimulation of the Na § § exchanger was secondary to cytosolic alkalinization, rather than the increase in intracellular Na + concentration (Grinstein & Goetz, 1985;Siffert & Akkerman, 1987).…”

Section: Discussionmentioning

confidence: 97%

Role of Na+/Ca2+ exchange and the plasma membrane Ca2+ pump in hormone-mediated Ca2+ efflux from pancreatic acini

1988

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The relative contributions of the Na+/Ca2+ exchange and the plasma membrane Ca2+ pump to active Ca2+ efflux from stimulated rat pancreatic acini were studied. Na+ gradients across the plasma membrane were manipulated by loading the cells with Na+ or suspending the cells in Na+-free media. The rates of Ca2+ efflux were estimated from measurements of [Ca2+]i using the Ca2+-sensitive fluorescent dye Fura 2 and 45Ca efflux. During the first 3 min of cell stimulation, the pattern of Ca2+ efflux is described by a single exponential function under control, Na+-loaded, and Na+-depleted conditions. Manipulation of Na+ gradients across the plasma membrane had minimal effects on resting [Ca2+]i, the rate constant of Ca2+ efflux, and [Ca2+]i levels attained by the cells after 5 min of stimulation. Changing Na+ gradients had no effect on the hormone-induced increase in [Ca2+]i. The results indicate that Ca2+ efflux from stimulated pancreatic acinar cells is mediated by the plasma membrane Ca2+ pump. The effects of several cations, which were used to substitute for Na+, on cellular activity were also studied. Choline+ and tetramethylammonium+ (TMA+) released Ca2+ from intracellular stores of pancreatic acinar, gastric parietal and peptic cells. These cations also stimulated enzyme and acid secretion from the cells. All effects of these cations were blocked by atropine. Measurements of cholecystokinin-octapeptide (CCK-OP)-stimulated amylase release from pancreatic acini, suspended in Na+, TMA+, choline+, or N-methyl-D-glucamine+ (NMG+) media containing atropine, were used to evaluate the effect of the cations on cellular function. NMG+, choline+, and TMA+ inhibited amylase release by 55, 40 and 14%, respectively. NMG+ also increased the Ca2+ permeability of the plasma membrane. Thus, to study Na+ dependency of cellular function, TMA+ is the preferred cation to substitute for Na+. The stimulatory effect of TMA+ can be blocked by atropine.

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Section: Discussionmentioning

confidence: 97%

Role of Na+/Ca2+ exchange and the plasma membrane Ca2+ pump in hormone-mediated Ca2+ efflux from pancreatic acini

1988

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“…We used amiloride at lower concentration (10 M) because it can inhibit not only ENaC but also NHEs at higher concentrations (Orlowski and Kandasamy, 1996;Praetorius et al, 2000). Furthermore, the Na ϩ -dependent Ca 2ϩ transport mechanism (presumably the Na ϩ /Ca 2ϩ exchanger) was shown to be functionally expressed in the rat submandibular gland Morris et al, 1987) and may be affected by amiloride. However, replacement of external Na ϩ with Li ϩ to inhibit Na ϩ /Ca 2ϩ exchanger activity (Blaustein and Santiago, 1977;Laskowski and Medler, 2009) failed to show any significant change in [Ca 2ϩ ] i in response to CCh, suggesting that it may be present in mouse submandibular gland, but it is not functionally important during muscarinic stimulation (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Cevimeline-Induced Monophasic Salivation from the Mouse Submandibular Gland: Decreased Na⁺Content in Saliva Results from Specific and Early Activation of Na⁺/H⁺Exchange

Kondo

Nakamoto²,

Mukaibo³

et al. 2011

J Pharmacol Exp Ther

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Cevimeline and pilocarpine are muscarinic agonists used clinically to treat dry mouth. In this study, we explored fluid secretion from mouse submandibular glands to determine the mechanism of cevimeline, pilocarpine, and an experimentally used agent carbachol. Cevimeline evoked almost the same amount of secretion at concentrations from 30 M to 1 mM. Pilocarpine also induced secretion at a concentration as low as 1 M and was the most powerful secretagogue at 10 M. Secretion was induced by carbachol at 0.1 M, with maximum secretion at 1.0 M. Cevimeline induced monophasic secretion at all concentrations tested, whereas higher concentrations of pilocarpine and carbachol induced secretion with variable kinetics, i.e., an initial transient high flow rate, followed by decreased secretion after 2 to 3 min. In the presence of an epithelial Na ϩ channel blocker, amiloride, neither carbachol nor pilocarpine affected the Na ϩ level of secreted saliva; however, it significantly increased the Na ϩ content of cevimeline-induced saliva. The intracellular Ca 2ϩ response of acinar cells was almost identical among all three agents, although recovery after drug removal was slower for cevimeline and pilocarpine. A profound decrease in intracellular pH was observed during pilocarpine and carbachol treatment, whereas intracellular acidification induced by cevimeline was only seen in the presence of a Na ϩ /H ϩ exchange inhibitor. When external HCO 3 Ϫ was removed, cevimeline-induced saliva significantly decreased. These findings suggest that cevimeline specifically activates Na ϩ /H ϩ exchange and may promote Na ϩ reabsorption by stabilizing epithelial sodium channel activity.

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“…Preliminary studies of the human sweat gland indicate that only the first of these phases is inhibited by removal of external sodium (Bovell, Elder, Jenkinson & Wilson, 1989 b). The sweat gland therefore appears to differ from the extensively studied rat submandibular gland where secretagogue-evoked calcium entry, but not mobilization, appears to be sodium dependent Morris, Fuller & Gallacher, 1987;Bovell, Elder, Pediani & Wilson, 1989c).…”

Section: Introductionmentioning

confidence: 97%

“…The sweat gland therefore appears to differ from the extensively studied rat submandibular gland where secretagogue-evoked calcium entry, but not mobilization, appears to be sodium dependent Morris, Fuller & Gallacher, 1987;Bovell, Elder, Pediani & Wilson, 1989c).…”

Section: Introductionmentioning

confidence: 99%

The effects of removing external sodium upon the control of potassium (86Rb+) permeability in the isolated human sweat gland

Wilson

Bovell²,

Elder³

et al. 1990

Experimental Physiology

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SUMMARYThe changes in cytoplasmic free calcium ([Ca2+]i) which occur in isolated human sweat glands during cholinergic stimulation have been studied indirectly by monitoring potassium permeability. The acetylcholine-evoked permeability increase normally consists of transient and sustained phases which are attributed to the mobilization of intracellular calcium stores and to calcium influx respectively. Such consistent responses to acetylcholine could not be obtained during superfusion with bicarbonate-free, HEPES-buffered solutions. The human sweat gland in vitro therefore appears to have a strict requirement for bicarbonate. The sustained component of the response was not affected by total removal of external sodium, suggesting that calcium influx does not occur via a sodium-dependent system. The transient component, however, was abolished when external sodium was replaced by N-methyl-Dglucammonium (NMDG+). It therefore appears that secretagogue-evoked mobilization of cytoplasmic calcium is dependent, in some way, upon external sodium. This dependence is not, however, absolute as the response was essentially normal when sodium was replaced by lithium.

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Cholinergic receptors regulate a voltage‐insensitive but Na⁺‐dependent calcium influx pathway in salivary acinar cells

Cited by 34 publications

References 14 publications

Role of Na+/Ca2+ exchange and the plasma membrane Ca2+ pump in hormone-mediated Ca2+ efflux from pancreatic acini

Role of Na+/Ca2+ exchange and the plasma membrane Ca2+ pump in hormone-mediated Ca2+ efflux from pancreatic acini

Cevimeline-Induced Monophasic Salivation from the Mouse Submandibular Gland: Decreased Na⁺Content in Saliva Results from Specific and Early Activation of Na⁺/H⁺Exchange

The effects of removing external sodium upon the control of potassium (86Rb+) permeability in the isolated human sweat gland

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Cholinergic receptors regulate a voltage‐insensitive but Na+‐dependent calcium influx pathway in salivary acinar cells

Cited by 34 publications

References 14 publications

Role of Na+/Ca2+ exchange and the plasma membrane Ca2+ pump in hormone-mediated Ca2+ efflux from pancreatic acini

Role of Na+/Ca2+ exchange and the plasma membrane Ca2+ pump in hormone-mediated Ca2+ efflux from pancreatic acini

Cevimeline-Induced Monophasic Salivation from the Mouse Submandibular Gland: Decreased Na+Content in Saliva Results from Specific and Early Activation of Na+/H+Exchange

The effects of removing external sodium upon the control of potassium (86Rb+) permeability in the isolated human sweat gland

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Cholinergic receptors regulate a voltage‐insensitive but Na⁺‐dependent calcium influx pathway in salivary acinar cells

Cevimeline-Induced Monophasic Salivation from the Mouse Submandibular Gland: Decreased Na⁺Content in Saliva Results from Specific and Early Activation of Na⁺/H⁺Exchange