scholarly journals HCO3− Secretion by Murine Nasal Submucosal Gland Serous Acinar Cells during Ca2+-stimulated Fluid Secretion

2008 ◽  
Vol 132 (1) ◽  
pp. 161-183 ◽  
Author(s):  
Robert J. Lee ◽  
Janice M. Harlow ◽  
Maria P. Limberis ◽  
James M. Wilson ◽  
J. Kevin Foskett
Keyword(s):  
Molecular Mechanisms ◽  
Driving Forces ◽  
Basolateral Membrane ◽  
Acinar Cells ◽  
Fluid Secretion ◽  
Cl Secretion ◽  
Cl Channel ◽  
Ion Substitution ◽  
Free Media ◽  
Nhe Isoforms

Airway submucosal glands contribute to airway surface liquid (ASL) composition and volume, both important for lung mucociliary clearance. Serous acini generate most of the fluid secreted by glands, but the molecular mechanisms remain poorly characterized. We previously described cholinergic-regulated fluid secretion driven by Ca2+-activated Cl− secretion in primary murine serous acinar cells revealed by simultaneous differential interference contrast (DIC) and fluorescence microscopy. Here, we evaluated whether Ca2+-activated Cl− secretion was accompanied by secretion of HCO3−, possibly a critical ASL component, by simultaneous measurements of intracellular pH (pHi) and cell volume. Resting pHi was 7.17 ± 0.01 in physiological medium (5% CO2–25 mM HCO3−). During carbachol (CCh) stimulation, pHi fell transiently by 0.08 ± 0.01 U concomitantly with a fall in Cl− content revealed by cell shrinkage, reflecting Cl− secretion. A subsequent alkalinization elevated pHi to above resting levels until agonist removal, whereupon it returned to prestimulation values. In nominally CO2–HCO3−-free media, the CCh-induced acidification was reduced, whereas the alkalinization remained intact. Elimination of driving forces for conductive HCO3− efflux by ion substitution or exposure to the Cl− channel inhibitor niflumic acid (100 μM) strongly inhibited agonist-induced acidification by >80% and >70%, respectively. The Na+/H+ exchanger (NHE) inhibitor dimethylamiloride (DMA) increased the magnitude (greater than twofold) and duration of the CCh-induced acidification. Gene expression profiling suggested that serous cells express NHE isoforms 1–4 and 6–9, but pharmacological sensitivities demonstrated that alkalinization observed during both CCh stimulation and pHi recovery from agonist-induced acidification was primarily due to NHE1, localized to the basolateral membrane. These results suggest that serous acinar cells secrete HCO3− during Ca2+-evoked fluid secretion by a mechanism that involves the apical membrane secretory Cl− channel, with HCO3− secretion sustained by activation of NHE1 in the basolateral membrane. In addition, other Na+-dependent pHi regulatory mechanisms exist, as evidenced by stronger inhibition of alkalinization in Na+-free media.

scholarly journals Gramicidin-perforated Patch Recording Revealed the Oscillatory Nature of Secretory Cl− Movements in Salivary Acinar Cells

2004 ◽  
Vol 124 (1) ◽  
pp. 59-69 ◽  
Author(s):  
Makoto Sugita ◽  
Chikara Hirono ◽  
Yoshiki Shiba
Keyword(s):  
Membrane Potential ◽  
Loop Diuretic ◽  
Basolateral Membrane ◽  
Acinar Cells ◽  
Fluid Secretion ◽  
Monovalent Cation ◽  
Free Calcium ◽  
Perforated Patch ◽  
Cl Channel ◽  
Cl Channels

Elevations of cytoplasmic free calcium concentrations ([Ca2+]i) evoked by cholinergic agonists stimulate isotonic fluid secretion in salivary acinar cells. This process is driven by the apical exit of Cl− through Ca2+-activated Cl− channels, while Cl− enters the cytoplasm against its electrochemical gradient via a loop diuretic-sensitive Na+-K+-2Cl− cotransporter (NKCC) and/or parallel operations of Cl−-HCO3− and Na+-H+ exchangers, located in the basolateral membrane. To characterize the contributions of those activities to net Cl− secretion, we analyzed carbachol (CCh)-activated Cl− currents in submandibular acinar cells using the “gramicidin-perforated patch recording configuration.” Since the linear polypeptide antibiotic gramicidin creates monovalent cation-selective pores, CCh-activated Cl− currents in the gramicidin-perforated patch recording were carried by Cl− efflux via Cl− channels, dependent upon Cl− entry through Cl− transporters expressed in the acinar cells. CCh-evoked oscillatory Cl− currents were associated with oscillations of membrane potential. Bumetanide, a loop diuretic, decreased the CCh-activated Cl− currents and hyperpolarized the membrane potential. In contrast, neither methazolamide, a carbonic anhydrase inhibitor, nor elimination of external HCO3− had significant effects, suggesting that the cotransporter rather than parallel operations of Cl−-HCO3− and Na+-H+ exchangers is the primary Cl− uptake pathway. Pharmacological manipulation of the activities of the Ca2+-activated Cl− channel and the NKCC revealed that the NKCC plays a substantial role in determining the amplitude of oscillatory Cl− currents, while adjusting to the rate imposed by the Ca2+-activated Cl− channel, in the gramicidin-perforated patch configuration. By concerting with and being controlled by the cation steps, the oscillatory form of secretory Cl− movements may effectively provide a driving force for fluid secretion in intact acinar cells.

scholarly journals Electrogenic NBCe1 (SLC4A4), but not electroneutral NBCn1 (SLC4A7), cotransporter undergoes cholinergic-stimulated endocytosis in salivary ParC5 cells

2008 ◽  
Vol 295 (5) ◽  
pp. C1385-C1398 ◽  
Author(s):  
Clint Perry ◽  
David O. Quissell ◽  
Mary E. Reyland ◽  
Irina I. Grichtchenko
Keyword(s):  
Membrane Trafficking ◽  
Basolateral Membrane ◽  
Fluorescent Microscopy ◽  
Acinar Cells ◽  
Fluid Secretion ◽  
Parotid Glands ◽  
Calmodulin Antagonist ◽  
Parotid Acinar Cells ◽  
Early Endosomes ◽  
Gf 109203X

Cholinergic agonists are major stimuli for fluid secretion in parotid acinar cells. Saliva bicarbonate is essential for maintaining oral health. Electrogenic and electroneutral Na+-HCO3− cotransporters (NBCe1 and NBCn1) are abundant in parotid glands. We previously reported that angiotensin regulates NBCe1 by endocytosis in Xenopus oocytes. Here, we studied cholinergic regulation of NBCe1 and NBCn1 membrane trafficking by confocal fluorescent microscopy and surface biotinylation in parotid epithelial cells. NBCe1 and NBCn1 colocalized with E-cadherin monoclonal antibody at the basolateral membrane (BLM) in polarized ParC5 cells. Inhibition of constitutive recycling with the carboxylic ionophore monensin or the calmodulin antagonist W-13 caused NBCe1 to accumulate in early endosomes with a parallel loss from the BLM, suggesting that NBCe1 is constitutively endocytosed. Carbachol and PMA likewise caused redistribution of NBCe1 from BLM to early endosomes. The PKC inhibitor, GF-109203X, blocked this redistribution, indicating a role for PKC. In contrast, BLM NBCn1 was not downregulated in parotid acinar cells treated with constitutive recycling inhibitors, cholinergic stimulators, or PMA. We likewise demonstrate striking differences in regulation of membrane trafficking of NBCe1 vs. NBCn1 in resting and stimulated cells. We speculate that endocytosis of NBCe1, which coincides with the transition to a steady-state phase of stimulated fluid secretion, could be a part of acinar cell adjustment to a continuous secretory response. Stable association of NBCn1 at the membrane may facilitate constitutive uptake of HCO3− across the BLM, thus supporting HCO3− luminal secretion and/or maintaining acid-base homeostasis in stimulated cells.

Regulation of electrolyte and fluid secretion in salivary acinar cells

1992 ◽  
Vol 263 (6) ◽  
pp. G823-G837 ◽  
Author(s):  
B. Nauntofte
Keyword(s):  
Ionic Composition ◽  
Basolateral Membrane ◽  
Acinar Cells ◽  
Fluid Secretion ◽  
Receptor Activation ◽  
Exchange Mechanism ◽  
Luminal Membrane ◽  
Net Uptake ◽  
Cl Channels ◽  
Simultaneous Activation

The primary secretion from exocrine gland cells is a fluid rich in Na+ and Cl- with a plasmalike ionic composition. Activation of specific receptors on the plasma membrane by hormones and neurotransmitters, which leads to activation of the phosphoinositol metabolism, results in release of Ca2+ from internal Ca2+ stores. Intracellular free Ca2+ concentration ([Ca2+]i) then rises simultaneously at both the basolateral and luminal parts of the acinar cell, reaching maximum values within 1 s after stimulation. In parotid acinar cells, increased [Ca2+]i activates the opening of maxi K+ channels located on the basolateral membrane and Cl- channels presumably located on the luminal membrane, resulting in rapid loss of K+ and Cl- and water and cell shrinkage. Extracellular electroneutrality is maintained by a paracellular Na+ flux into the lumen. Because of the simultaneous activation of K+ and Cl- channels, secretion occurs at a virtually constant membrane potential of about -60 mV. After maximal muscarinic cholinergic stimulation, loss of K+, Cl-, and water results in an approximate 25% reduction in cell volume within 10-15 s after receptor activation. Concomitant with loss of Cl-, there is a loss of HCO3- from the cell, causing a decrease in intracellular pH of 0.1 pH units because of the carbonic anhydrase-mediated conversion of CO2 into H+ and HCO3-. H+ generated from the metabolism and HCO3- production is compensated for by extrusion of H+ by a Na(+)-H+ exchange mechanism, which is responsible for approximately 75% of net Na+ gain that occurs after stimulation. Increased [Na+]i activates the Na(+)-K+ pump, which in turn extrudes Na+ from the cells. In both the unstimulated and stimulated states, cellular production of HCO3- can drive a net uptake of Cl- via the Cl(-)-HCO3- exchange mechanism operating in parallel with the Na(+)-H+ exchanger. The operation of the Cl(-)-HCO3- exchanger is, together with a Na(+)-K(+)-2Cl- cotransport system, essential for maintainance of a high [Cl-]i both in the unstimulated state and during Cl- reuptake.

Psoralens: novel modulators of Cl- secretion

1997 ◽  
Vol 272 (3) ◽  
pp. C976-C988 ◽  
Author(s):  
D. C. Devor ◽  
A. K. Singh ◽  
R. J. Bridges ◽  
R. A. Frizzell
Keyword(s):  
Short Circuit ◽  
Basolateral Membrane ◽  
Primary Cultures ◽  
Receptor Activation ◽  
Sustained Response ◽  
Rat Colon ◽  
Cl Secretion ◽  
Cl Channel ◽  
Cl Channels ◽  
Cl Conductance

We evaluated effects of psoralens on Cl- secretion (short-circuit current, I(sc)) across T84 monolayers. Methoxsalen failed to increase I(sc). Several observations suggest that psoralens open cystic fibrosis transmembrane conductance regulator Cl- channels. 1) After activation of the Ca2+-dependent basolateral membrane K+ channel (K(Ca)) by 1-ethyl-2-benzimidazolinone or thapsigargin, methoxsalen (10 microM) further increased I(sc). 2) When added before carbachol (CCh), methoxsalen potentiated the I(sc) response to CCh, as predicted, if it increased apical Cl- conductance. 3) After establishment of a mucosal-to-serosal Cl- gradient and permeabilization of basolateral membrane with nystatin, psoralens increased Cl- current, which was inhibited by glibenclamide. In contrast, neither TS-TM calix[4]arene nor Cd2+, inhibitors of outwardly rectifying Cl- channels and the ClC-2 Cl-channel, respectively, inhibited psoralen-induced Cl- current. In contrast to their effects on Cl- conductance, psoralens failed to significantly affect basolateral membrane K+ conductance; subsequent addition of 1-ethyl-2-benzimidazolinone induced a large increase in K+ conductance. Also, in excised patches, methoxsalen failed to activate K(Ca). In addition to potentiating the peak response to CCh, psoralens induced a secondary, sustained response. Indeed, when added up to 60 min after return of CCh-induced I(sc) to baseline, psoralens induced a sustained I(sc). This sustained response was inhibited by atropine, demonstrating the requirement for continuous muscarinic receptor activation by CCh. This sustained response was inhibited also by verapamil, removal of bath Ca2+, and charybdotoxin. These results suggest that return of I(sc) to baseline after CCh stimulation is not due to downregulation of Ca2+ influx or K(Ca). Finally, we obtained similar results with psoralens in rat colon and primary cultures of murine tracheal epithelium. On the basis of these observations, we conclude that psoralens represent a novel class of Cl- channel openers that can be used to probe mechanisms underlying Ca2+-mediated Cl- secretion.

Potassium transport across basolateral membrane of acinar cells in the perfused rat pancreas

1991 ◽  
Vol 261 (4) ◽  
pp. G570-G577
Author(s):  
T. Ishikawa ◽  
T. Kanno
Keyword(s):  
Basolateral Membrane ◽  
Acinar Cells ◽  
Fluid Secretion ◽  
Potassium Transport ◽  
Perfused Rat Pancreas ◽  
Complete Replacement ◽  
Rat Pancreas ◽  
Initial Transient ◽  
K Concentration ◽  
K Transport

Efflux and influx of K+ across the basolateral membrane of acinar cells were continuously computed from the change in K+ concentration in the perfusate collected from the portal vein of the isolated perfused rat pancreas. Continuous stimulation with different concentrations of COOH-terminal octapeptide of cholecystokinin (CCK-8) caused characteristic patterns of K+ flux and fluid secretion as follows: 1) stimulation with 10 pM CCK-8 induced a gradual and small increase in K+ influx and sustained fluid secretion; 2) stimulation with 100 pM CCK-8 caused an initial transient K+ efflux followed by a secondary slow K+ influx and sustained fluid secretion; 3) stimulation with 1 nM CCK-8 also induced an initial transient K+ efflux followed by a secondary slow K+ influx, whereas there was only a slight transient increase in fluid secretion. Ouabain abolished the CCK-8-induced K+ influx, but furosemide had little, if any, effect on the CCK-8-induced K+ flux and fluid secretion. Complete replacement of Cl- with equimolar NO3- had little effect on the CCK-8-induced K+ influx. These results suggest that CCK-8 activates not only passive K+ transport but also an ouabain sensitive Na(+)-K+ pump and that the furosemide-sensitive Na(+)-K(+)-2Cl- symport may not play a significant role in CCK-8-induced K+ transport.

Mechanisms of Ca2+-stimulated fluid secretion by porcine bronchial submucosal gland serous acinar cells

2010 ◽  
Vol 298 (2) ◽  
pp. L210-L231 ◽  
Author(s):  
Robert J. Lee ◽  
J. Kevin Foskett
Keyword(s):  
Basolateral Membrane ◽  
Acinar Cells ◽  
Fluid Secretion ◽  
Cell Swelling ◽  
Solute Content ◽  
Intracellular Ca ◽  
Shrinkage And Swelling ◽  
Serous Cell ◽  
Rat Parotid ◽  
Necessary And Sufficient

The serous acini of airway submucosal glands are important for fluid secretion in the lung. Serous cells are also sites of expression of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channel. However, the mechanisms of serous cell fluid secretion remain poorly defined. In this study, serous acinar cells were isolated from porcine bronchi and studied using optical techniques previously used to examine fluid secretion in rat parotid and murine nasal acinar cells. When stimulated with the cholinergic agonist carbachol, porcine serous cells shrank by ∼20% (observed via DIC microscopy) after a profound elevation of intracellular [Ca2+] ([Ca2+]i; measured by simultaneous fura 2 fluorescence imaging). Upon removal of agonist and relaxation of [Ca2+]i to resting levels, cells swelled back to resting volume. Similar results were observed during stimulation with histamine and ATP, and elevation of [Ca2+]i was found to be necessary and sufficient to activate shrinkage. Cell volume changes were associated with changes in [Cl−]i (measured using SPQ fluorescence), suggesting that shrinkage and swelling are caused by loss and gain of intracellular solute content, respectively, likely reflecting changes in the secretory state of the cells. Shrinkage was inhibited by niflumic acid but not by GlyH-101, suggesting Ca2+-activated secretion is mediated by alternative non-CFTR Cl− channels, possibly including Ano1 (TMEM16A), expressed on the apical membrane of porcine serous cells. Optimal cell swelling/solute uptake required activity of the Na+K+2Cl− cotransporter and Na+/H+ exchanger, both of which are expressed on the basolateral membrane of serous acini and likely contribute to sustaining transepithelial secretion.

Apical and basolateral ATP stimulates tracheal epithelial chloride secretion via multiple purinergic receptors

1996 ◽  
Vol 270 (6) ◽  
pp. C1611-C1623 ◽  
Author(s):  
T. H. Hwang ◽  
E. M. Schwiebert ◽  
W. B. Guggino
Keyword(s):  
Cystic Fibrosis ◽  
Purinergic Receptors ◽  
Basolateral Membrane ◽  
Receptor Subtypes ◽  
Cl Secretion ◽  
Cl Channel ◽  
Basolateral Side ◽  
Channel Blocking ◽  
Cl Channels ◽  
Tracheal Epithelial

Stimulation of Cl- secretion across the airway epithelium by ATP or UTP as agonists has therapeutic implications for cystic fibrosis. Our results demonstrate that ATP stimulates Cl- secretion in rat tracheal epithelial cell monolayers in primary culture from the apical or basolateral side of the monolayer. Multiple types of ATP-sensitive Cl- conductances in intact monolayers were elucidated through inhibition by Cl- channel-blocking drugs. Multiple Cl- conductances stimulated by ATP and adenosine 3',5'-cyclic monophosphate (cAMP) (tested for comparison) were also deciphered more specifically by nystatin permeabilization of the basolateral membrane, subsequent imposition of symmetrical Cl-, I-, or Br- solutions to test halide permselectivity, inhibition by Cl- channel-blocking drugs, and construction of current-voltage plots to study time and voltage dependence of the currents. Apical ATP stimulates Cl- secretion through P2U (or P2Y2) purinergic receptors via both intracellular Ca2+ (Ca(2+)i)-dependent and Cai(2+)-independent signaling pathways by opening outwardly rectifying Cl- channels (ORCCs), cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channels, and Cai(2+)-dependent Cl- channels. Basolateral ATP stimulates Cl- secretion via a combination of receptor subtypes (P2T and P2U) or a novel type of receptor (P2Y3), independent of Cai2+ or cAMP signaling by opening only CFTR channels. cAMP also stimulated multiple types of Cl- conductances, consistent with simultaneous activation of CFTR and ORCCs. Together, these results suggest that ATP as an agonist stimulates Cl- secretion via multiple purinergic receptors and multiple signal transduction pathways activated in different membrane domains of tracheal epithelia.

Ion transport across the jejunum in normal and cystic fibrosis mice

1995 ◽  
Vol 268 (3) ◽  
pp. G505-G513 ◽  
Author(s):  
B. R. Grubb
Keyword(s):  
Cystic Fibrosis ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Fluid Secretion ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Targeted Disruption ◽  
Cl Secretion ◽  
Ion Substitution ◽  
Cystic Fibrosis Transmembrane

Cystic fibrosis (CF) mice created by targeted disruption of the murine cystic fibrosis transmembrane conductance regulator gene lack adenosine 3',5'-cyclic monophosphate (cAMP)-mediated Cl- secretion and exhibit marked intestinal complications secondary to inadequate fluid secretion. The basal short-circuit current (Isc) in the normal murine jejuna [43.2 +/- 5.9 microA.cm-2, n = 10 (mean +/- SE)] exhibits marked spontaneous n = 10 (mean +/- SE)] exhibits marked spontaneous oscillations (amplitude = 47.9 microA.cm-2, n = 18), which were completely absent in the CF jejunum. Treatment of normal jejuna with the neuronal blocker tetrodotoxin completely eliminated the oscillations and decreased the Isc to levels not significantly different from the low basal Isc (5.4 +/- 2.8 microA.cm-2, n = 16) exhibited by CF tissue. Ion substitution studies revealed basal Isc in normal jejuna to be due primarily to Cl- secretion but these tissues appeared to be capable of HCO3- secretion as well. In contrast, CF jejuna spontaneously secreted neither Cl- nor HCO3-, which may indicate that CF jejuna have a defect in the ability to secrete both of these anions. Apical glucose elicited an electrogenic absorption of Na+ of identical magnitude in normal and CF jejuna. Without apical glucose, CF jejuna exhibited a very small Isc response to forskolin (delta 2.2 +/- 0.67 microA.cm-2, n = 10). However, in the presence of apical glucose, forskolin elicited an eightfold greater Isc response in the CF tissue (delta 17.2 +/- 4.8 microA.cm-2, n = 9).(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium-activated potassium channels and fluid secretion by exocrine glands

1986 ◽  
Vol 251 (1) ◽  
pp. G1-G13 ◽  
Author(s):  
O. H. Petersen
Keyword(s):  
Single Channel ◽  
Basolateral Membrane ◽  
Acinar Cells ◽  
Fluid Secretion ◽  
Exocrine Glands ◽  
K Channels ◽  
Luminal Membrane ◽  
Channel Opening ◽  
Cell Current ◽  
Cl Channels

Fluid secretion by exocrine glands is regulated by neurotransmitters and hormones. The secretagogues act on the acinar cells by switching on two types of conductance pathways: K+-selective channels in the basolateral membrane and Cl(-)-selective channels localized to the luminal membrane. The K+ channels have been quantitatively characterized in patch-clamp single-channel and whole-cell current-recording studies. Opening of the K+ channels is determined by the membrane potential (depolarization enhances the probability of channel opening), and the intracellular free Ca2+ concentration ([Ca2+]i) (a rise in [Ca2+]i increases the open-state probability). The Cl- channels are also controlled by internal Ca2+ in such a way that an elevation of [Ca2+]i favors opening. Secretagogues evoking an increase in [Ca2+]i activate both sets of channels causing a substantial loss of cellular KCl. KCl is taken up via a Na+-K+-2Cl- cotransport mechanism in the basolateral membrane and the Na+ uptake activates the Na+-K+ pump. In the steady-state stimulated situation the three basolateral transport proteins, the K+ channels, the Na+-K+ pump, and the Na+-K+-2Cl- cotransporter operate together as an electrogenic Cl- pump. Cl- exits into the lumen via the Ca2+-activated Cl- channels and Na+ follows through the paracellular shunt pathway. When stimulation of the acinar cells ceases the K+ and Cl- conductance pathways close and the Na+-K+ pump together with the Na+-K+-2Cl- cotransporter operate as a KCl pump, restoring the intracellular KCl lost initially after start of stimulation and secretion stops.

Activation of the Ae4 (Slc4a9) cation-driven Cl-/HCO3- exchanger by the cAMP-dependent protein kinase (PKA) in salivary gland acinar cells

2021 ◽  
Author(s):  
Gaspar Peña-Munzenmayer ◽  
Yusuke Kondo ◽  
Constanza Salinas ◽  
José Sarmiento ◽  
Sebastian Brauchi ◽  
...  
Keyword(s):  
Adrenergic Receptor ◽  
Basolateral Membrane ◽  
Acinar Cells ◽  
Homology Model ◽  
Fluid Secretion ◽  
Dependent Protein Kinase ◽  
Physiological Regulation ◽  
Terminal Domain ◽  
Dependent Protein ◽  
Dependent Signaling Pathway

Ae4 transporters are critical for Cl- uptake across the basolateral membrane of acinar cells in the submandibular gland (SMG). Although required for fluid secretion, little is known about the physiological regulation of Ae4. To investigate whether Ae4 is regulated by the cAMP-dependent signaling pathway, we measured Cl-/HCO3- exchanger activity in SMG acinar cells from Ae2-/- mice, which only express Ae4, and found that the Ae4-mediated activity was increased in response to β-adrenergic receptor stimulation. Moreover, pretreatment with H89, an inhibitor of the cAMP-activated kinase (PKA), prevented the stimulation of Ae4 exchangers. We then expressed Ae4 in CHO-K1 cells and found that the Ae4-mediated activity was increased when Ae4 is co-expressed with the catalytic subunit of PKA (PKAc), which is constitutively active. Ae4 sequence analysis showed two potential PKA phosphorylation serine residues located at the intracellular N-terminal domain according to a homology model of Ae4. N-terminal domain Ser residues were mutated to alanine (S173A and S273A, respectively), where the Cl-/HCO3- exchanger activity displayed by the mutant S173A was not activated by PKA. Conversely, S273A mutant kept the PKA dependency. Together, we conclude that Ae4 is stimulated by PKA in SMG acinar cells by a mechanism that probably depends on the phosphorylation of S173.

Sign in / Sign up

Export Citation Format

Share Document