Potentiation by Isoproterenol on Carbachol-induced K + and Cl − Currents and Fluid Secretion in Rat Parotid

Hirono, Chikara; Sugita, Makoto; Furuya, Kishio; Yamagishi, Shunichi; Shiba, Yoshiki

doi:10.1007/s002329900405

Cited by 28 publications

(28 citation statements)

References 19 publications

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“…The Ca 2+ -sensitive adenylyl cyclase (type 8) is reported to be critical for accumulation of cAMP in mouse parotid acinar cells (Watson et al 2000 An interaction between the cAMP and the Ca 2+ signal has been reported to regulate various cellular functions. In salivary glands, cAMP modulates Ca 2+ entry (Tanimura et al 1999;Nakahari et al 2000), K + and Cl _ channels (Ishikawa, 1997), fluid secretion (Hirono et al 1998) and exocytosis (Yoshimura & Nezu, 1992;Nakahari et al 2000), which are all activated by increases in [Ca 2+ ] i . While these studies showed that cAMP modulates the action of Ca 2+ , in our study Ca 2+ modulates the action of cAMP.…”

Section: Figure 10mentioning

confidence: 99%

EP1 and EP4 Receptors Mediate Exocytosis Evoked by Prostaglandin E₂ in Guinea‐Pig Antral Mucous Cells

Ohnishi

Shimamoto

Katsu

et al. 2001

Experimental Physiology

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Effects of prostaglandin E2 (PGE2) on exocytosis of mucin were studied in mucous cells isolated from guinea‐pig antrum using video‐microscopy. Stimulation with PGE2 elicited a sustained increase in the frequency of exocytotic events in a dose‐dependent manner, which was under regulation by both Ca2+ and cAMP. Stimulation with a selective prostanoid EP4 receptor agonist (ONO‐AEI‐329, 10 μM), which activates cAMP signals, elicited a sustained increase in the frequency of exocytotic events (30% of that evoked by 1 μM PGE2). Stimulation with an EP1 agonist (17‐P‐T‐PGE2, 1 μM), which activates Ca2+ signals, increased the frequency of exocytotic events to a lesser extent (5% of that evoked by 1 μM PGE2), while addition of an EP1 antagonist (ONO‐8713, 10 μM) decreased the frequency of exocytotic events (approximately 40% of that evoked by 1 μM PGE2). However, addition of the EP1 agonist potentiated the frequency of exocytotic events evoked by the EP4 agonist or forskolin (which elevates cAMP levels) and increased the sensitivity of the exocytotic events to forskolin. These results suggest that the Ca2+ signal activated via the EP1 receptor potentiates the cAMP‐regulated exocytotic events activated via the EP4 receptor during PGE2 stimulation, by increasing the sensitivity of the exocytotic response to cAMP. In conclusion, exocytotic events in PGE2‐stimulated antral mucous cells were regulated by interactions between EP1 and EP4 receptors.

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Section: Figure 10mentioning

confidence: 99%

EP1 and EP4 Receptors Mediate Exocytosis Evoked by Prostaglandin E₂ in Guinea‐Pig Antral Mucous Cells

Ohnishi

Shimamoto

Katsu

et al. 2001

Experimental Physiology

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“…InsP 3 R2 is the major InsP 3 R isoform in many cell types, including hepatocytes (7,8), astrocytes (9,10), cardiac myocytes (11), and exocrine acinar cells (8,12). Activation of PKA has been demonstrated to enhance InsP 3 -induced Ca 2ϩ signaling in hepatocytes (13) and parotid acinar cells (4,14). Although PKA phosphorylation of InsP 3 R2 is a likely causal mechanism underlying these effects, the functional effects of phosphorylation have not been determined in cells unambiguously expressing InsP 3 R2 in isolation.…”

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confidence: 99%

Protein Kinase A Increases Type-2 Inositol 1,4,5-Trisphosphate Receptor Activity by Phosphorylation of Serine 937

Betzenhauser

Fike

Wagner

et al. 2009

Journal of Biological Chemistry

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Hormones, neurotransmitters, and growth factors stimulate the production of InsP 3 3 and Ca 2ϩ signals in virtually all cell types (1). The ubiquitous nature of this mode of signaling dictates that this pathway does not exist in isolation; indeed, a multitude of additional signaling pathways can be activated simultaneously. A prime example of this type of "cross-talk" between independently activated signaling systems results from the parallel activation of cAMP and Ca 2ϩ signaling pathways (2, 3). Interactions between these two systems occur in numerous distinct cell types with various physiological consequences (3-6). Given the central role of InsP 3 R in Ca 2ϩ signaling, a major route of modulating the spatial and temporal features of Ca 2ϩ signals following cAMP production is potentially through PKA phosphorylation of the InsP 3 R isoform(s) expressed in a particular cell type. There are three InsP 3 R isoforms (InsP 3 R1, InsP 3 R2, and InsP 3 R3) expressed to varying degrees in mammalian cells (7,8). InsP 3 R1 is the major isoform expressed in the nervous system, but it is less abundant compared with other subtypes in non-neuronal tissues (8). Ca 2ϩ release via InsP 3 R2 and InsP 3 R3 predominate in these tissues. InsP 3 R2 is the major InsP 3 R isoform in many cell types, including hepatocytes (7, 8), astrocytes (9, 10), cardiac myocytes (11), and exocrine acinar cells (8,12). Activation of PKA has been demonstrated to enhance InsP 3 -induced Ca 2ϩ signaling in hepatocytes (13) and parotid acinar cells (4,14). Although PKA phosphorylation of InsP 3 R2 is a likely causal mechanism underlying these effects, the functional effects of phosphorylation have not been determined in cells unambiguously expressing InsP 3 R2 in isolation. Furthermore, the molecular determinants of PKA phosphorylation of this isoform are not known.PKA-mediated phosphorylation is an efficient means of transiently and reversibly regulating the activity of the InsP 3 R. InsP 3 R1 was identified as a major substrate of PKA in the brain prior to its identification as the InsP 3 R (15, 16). However, until recently, the functional consequences of phosphorylation were unresolved. Initial conflicting results were reported indicating that phosphoregulation of InsP 3 R1 could result in either inhibition or stimulation of receptor activity (16,17). Mutagenic strategies were employed by our laboratory to clarify this discrepancy. These studies unequivocally assigned phosphorylation-dependent enhanced Ca 2ϩ release and InsP 3 R1 activity at the single channel level, through phosphorylation at canonical PKA consensus motifs at Ser 1589 and Ser 1755 . The sites responsible were also shown to be specific to the particular InsP 3 R1 splice variant (18). These data were also corroborated by replacing the relevant serines with glutamates in a strategy designed to construct "phosphomimetic" InsP 3 R1 by mimicking the negative charge added by phosphorylation (19,20). Of particular note, however, although all three isoforms are substrates for PKA, neither o...

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“…Indeed, the dilute secretion elicited by parasympathetic stimulation in situ (or muscarinic cholinergic agonists in vitro) contains a protein content, whereas the protein-rich, low volume secretion produced by ␤-adrenergic agonists contains fluid and electrolytes. Furthermore, parasympathetically and sympathetically controlled signaling pathways are synergistic in enhancing the rates of protein export and fluid and electrolyte transport (4,(7)(8)(9)(10). Thus alone and in combination, the signaling pathways enable acinar cells to vary the amount and composition of saliva over a wide range.…”

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confidence: 99%

Resting (Basal) Secretion of Proteins Is Provided by the Minor Regulated and Constitutive-like Pathways and Not Granule Exocytosis in Parotid Acinar Cells

Huang

Castle

Hinton

et al. 2001

Journal of Biological Chemistry

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Resting secretion of salivary proteins by the parotid gland is sustained in situ between periods of eating by parasympathetic stimulation and has been assumed to involve low level granule exocytosis. By using parotid lobules from ad libitum fed rats stimulated with low doses of carbachol as an in vitro analog of resting secretion, we deduce from the composition of discharged proteins that secretion does not involve granule exocytosis. Rather, it derives from two other acinar export routes, the constitutive-like (stimulus-independent) pathway and the minor regulated pathway, which responds to low doses of cholinergic or ␤-adrenergic agonists (Castle, J. D., and Castle, A. M. (1996) J. Cell Sci. 109, 2591-2599). The protein composition collected in vitro mimics that collected from cannulated ducts of glands given low level stimulation in situ. Analysis of secretory trafficking along the two pathways of resting secretion has indicated that the constitutive-like pathway may pass through endosomes after diverging from the minor regulated pathway at a brefeldin A-sensitive branch point. The branch point is deduced to be distal to a common vesicular budding event by which both pathways originate from immature granules. Detectable perturbation of neither pathway in lobules was observed by wortmannin addition, and neither serves as a significant export route for lysosomal procathepsin B. These findings show that parotid acinar cells use low capacity, high sensitivity secretory pathways for resting secretion and reserve granule exocytosis, a high capacity, low sensitivity pathway, for massive salivary protein export during meals. An analogous strategy may be employed in other secretory cell types.Salivary acinar cells are highly polarized epithelial cells that are specialized for the secretion of the macromolecular, electrolyte, and fluid components of saliva. Macromolecular secretion is achieved by the intracellular transport pathway, culminating in exocytosis of post-Golgi carriers at the apical plasma membrane. In contrast, export of electrolytes and fluid is achieved by a transepithelial flux of ions and passive flow of water mediated by specific membrane-associated pumps and channels. Secretion is mostly neurally regulated with the discharge of macromolecules and of electrolytes and fluid being controlled differentially (1). In the parotid gland, the rate of macromolecular (mostly protein) secretion is mainly controlled by sympathetic stimulation through ␤-adrenergic receptors. Rates of fluid and electrolyte secretion are mainly controlled by parasympathetic stimulation through muscarinic acetylcholine receptors and, to a lesser extent, sympathetic stimulation through ␣-adrenergic receptors (see Refs. 2-4 and reviewed in Refs. 5 and 6). Although these are the primary divisions in secretory signaling, they are not absolute. Indeed, the dilute secretion elicited by parasympathetic stimulation in situ (or muscarinic cholinergic agonists in vitro) contains a protein content, whereas the protein-rich, low volume secretion...

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Potentiation by Isoproterenol on Carbachol-induced K + and Cl − Currents and Fluid Secretion in Rat Parotid

Cited by 28 publications

References 19 publications

EP1 and EP4 Receptors Mediate Exocytosis Evoked by Prostaglandin E₂ in Guinea‐Pig Antral Mucous Cells

EP1 and EP4 Receptors Mediate Exocytosis Evoked by Prostaglandin E₂ in Guinea‐Pig Antral Mucous Cells

Protein Kinase A Increases Type-2 Inositol 1,4,5-Trisphosphate Receptor Activity by Phosphorylation of Serine 937

Resting (Basal) Secretion of Proteins Is Provided by the Minor Regulated and Constitutive-like Pathways and Not Granule Exocytosis in Parotid Acinar Cells

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Potentiation by Isoproterenol on Carbachol-induced K + and Cl − Currents and Fluid Secretion in Rat Parotid

Cited by 28 publications

References 19 publications

EP1 and EP4 Receptors Mediate Exocytosis Evoked by Prostaglandin E2 in Guinea‐Pig Antral Mucous Cells

EP1 and EP4 Receptors Mediate Exocytosis Evoked by Prostaglandin E2 in Guinea‐Pig Antral Mucous Cells

Protein Kinase A Increases Type-2 Inositol 1,4,5-Trisphosphate Receptor Activity by Phosphorylation of Serine 937

Resting (Basal) Secretion of Proteins Is Provided by the Minor Regulated and Constitutive-like Pathways and Not Granule Exocytosis in Parotid Acinar Cells

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EP1 and EP4 Receptors Mediate Exocytosis Evoked by Prostaglandin E₂ in Guinea‐Pig Antral Mucous Cells

EP1 and EP4 Receptors Mediate Exocytosis Evoked by Prostaglandin E₂ in Guinea‐Pig Antral Mucous Cells