Beta‐adrenergic receptor mechanisms in rat parotid glands: activation by nerve stimulation and 3‐isobutyl‐1‐methylxanthine.

Fuller, Catherine M.; Gallacher, D V

doi:10.1113/jphysiol.1984.sp015468

Cited by 17 publications

(12 citation statements)

References 20 publications

(29 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4 A), indicating that it is associated with the increased intracellular cAMP levels known to occur following fl-adrenergic stimulation of this tissue (24, 25,30). The dose ofisoproterenol yielding a halfmaximal effect on the cotransporter (2.15 X IO-' M; Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, since atenolol (a specific #I antagonist) blocks the effect of isoproterenol, and since both epinephrine (a combined fA and f2 adrenergic agonist) and norepinephrine (a relatively specific Il agonist) mimic the effect of isoproterenol at comparable doses (Fig. 5), it appears that this upregulation, like amylase release (23,30,31), is mediated via the f,8 adrenoreceptor subtype (32). The fact that the effect of isoproterenol is blocked by the protein kinase inhibitors H9, staurosporine and K252a (Fig.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Beta-adrenergic upregulation of the Na(+)-K(+)-2Cl- cotransporter in rat parotid acinar cells.

Paulais¹,

Turner²

1992

J. Clin. Invest.

View full text Add to dashboard Cite

We used the pH-sensitive fluorescent dye 2',7'-bis(2-carboxyethyl)-5(6')-carboxyfluorescein to monitor the recovery of the intracellular pH (pH,) of rat parotid acini from an NH+-induced alkaline load. This recovery was markedly inhibited by the loop diuretic bumetanide and by Cl-removal, indicating that it is largely due to NH' entry via the basolateral Na'-K+-2Cl-cotransporter. The rate of recovery of pHi was enhanced threefold by pretreatment (37.5 s) with isoproterenol (K112 = 21.5 nM) or norepinephrine (in the presence of phentolamine), and blocked by the #,-specific antagonist atenolol, indicating an upregulation of cotransport activity by ,81-adrenergic stimulation. The effect of isoproterenol was prevented by protein kinase inhibitors and mimicked by cAMP analogues, and by maneuvers known to increase cytosolic cAMP levels in these cells, consistent with the involvement ofprotein kinase A. Physiologically, such an upregulation of the acinar Na'-K+-2CI-cotransporter would lead to an increase in acinar chloride uptake across the basolateral membrane, and consequently, an increase in overall chloride and fluid secretion. Prevention of this upregulation by t-blockers and possibly by other commonly used clinical agents may account for the dry mouth and dry eyes experienced by some patients taking these medications. (J.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Beta-adrenergic upregulation of the Na(+)-K(+)-2Cl- cotransporter in rat parotid acinar cells.

Paulais¹,

Turner²

1992

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…Parotid acinar cells treated with a combination of H-89 (10 M) and Rp-cAMPS (30 M), an inhibitor combination that was effective in blocking different PKA-mediated effects (34) in mouse parotid acinar cells (14), did not restore the carbacholpromoted increase in ERK phosphorylation in cells treated with isoproterenol (Fig. 6).…”

Section: Pka Inhibitors Affect Erk Phosphorylation By Carbachol-mentioning

confidence: 99%

“…Inhibitory Effects of Isoproterenol Are Mediated by the ␤-Adrenergic Receptor-Although isoproterenol is a ␤-adrenergic receptor ligand known to increase cAMP in rat parotid gland (34), it was possible that its inhibitory actions on ERK phosphorylation were due to an off-target effect. Therefore, we determined whether propranolol, a ␤-adrenergic receptor antagonist, blocked the inhibitory effects of isoproterenol.…”

Section: Isoproterenol Rapidly Blocks Erk Phosphorylation Promotedmentioning

confidence: 99%

Isoproterenol and cAMP Block ERK Phosphorylation and Enhance [Ca2+] Increases and Oxygen Consumption by Muscarinic Receptor Stimulation in Rat Parotid and Submandibular Acinar Cells

Soltoff

Hedden

2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

Salivary glands are innervated by sympathetic and parasympathetic neurons, which release neurotransmitters that promote fluid secretion and exocytosis when they bind to muscarinic and ␤-adrenergic receptors, respectively. Signaling pathways downstream of these receptors are mainly distinct, but there is cross-talk that affects receptor-dependent events. Here we report that the ␤-adrenergic ligand isoproterenol blocks increases in extracellular signal-related kinase (ERK) phosphorylation, a protein kinase C-dependent event promoted by the muscarinic receptor ligand carbachol in freshly dispersed rat parotid acinar cells. The inhibitory action of isoproterenol was reproduced by cAMP stimuli ( Almost all mammalian cells have multiple types of heptahelical G-protein-coupled receptors. The muscarinic receptor and ␤-adrenergic receptor are G-protein-coupled receptors that affect the physiological activities of many cells, and neurotransmitters binding to these receptors produce well defined and mainly separate functional effects in salivary glands, which are innervated by both sympathetic and parasympathetic neurons (1). Parotid acinar cells express M3 muscarinic receptors (2), which are coupled via G q to phospholipase C, and acetylcholine and M3R 2 ligands binding to this receptor initiate the production of the second messengers inositol trisphosphate (InsP 3 ) and diacylglycerol, which elevate the intracellular Ca 2ϩ concentration ([Ca 2ϩ ] i ) and activate PKC. The increase in intracellular Ca 2ϩ initiates the opening of ion channels, electrolyte and fluid secretion, and subsequently, the formation of saliva in the oral cavity (3). In contrast, the activation of parotid ␤-adrenergic receptors promotes exocytosis and the release of amylase protein into the oral cavity. ␤-Adrenergic receptors are coupled via G s to adenylyl cyclase, and receptor stimulation generates the production of cAMP (cyclic adenosine monophosphate) and the activation of cAMP-dependent protein kinase (protein kinase A (PKA)) and a signaling cascade downstream of PKA. Muscarinic receptors also can promote exocytosis, but this is more limited than that due to ␤-adrenergic signaling (4). In many cells cAMP also can activate exchange proteins directly activated by cAMP (Epac), which are guanine nucleotide exchange factors for the GTPase Rap. Epac is a cAMP-dependent PKA-independent protein that can mediate various signaling and functional events in salivary glands and other cells (5-7). This can produce complications in evaluating the mechanisms of cross-talk that exist when there is combined muscarinic and ␤-adrenergic signaling, which is a focus of the present study.Isoproterenol has other effects on parotid acinar cells in addition to promoting exocytosis of secretory granules. It

show abstract

“…Although elevation of the cyclic AMP concentration by a PDE inhibitor has been demonstrated previously in cultured salivary acinar cells 3 , to our knowledge there are no previous reports on in vivo examination of this phenomenon.…”

Section: Introductionmentioning

confidence: 61%

Changes in Salivary Gene Expression in F344 Rats Exposed to Theophylline

et al. 2006

View full text Add to dashboard Cite

Exposure to theophylline, a phosphodiesterase (PDE) inhibitor, increases the basophilic basal part and conspicuous nucleoli in salivary acini. These histological findings imply increased gene expression. The purpose of this study was to examine the effect of theophylline on the expression of representative genes in the salivary glands which are regulated by cyclic AMP. Male F344 rats received saline or theophylline (50 mg/kg) intraperitoneally. Parotid and submaxillary glands were isolated from rats at 4, 8, and 24 h post-administration, and gene expression for the principal secretory proteins, amylase 1 (AMY1) and cystatin S (CysS), dominant PDE subfamilies 3A and 4D, and a water channel, aquaporin 5 (AQP5) were quantified by RT-PCR. The cyclic AMP concentration was determined by enzyme-immunoassay. Theophylline exposure resulted in a transient increase in mRNA expression for AMY1 in the parotid gland, CysS in the submaxillary gland, and PDE3A in both salivary glands. The cyclic AMP concentration was elevated in both glands. PDE4D and AQP5 gene expressions were not altered in either gland. Our results suggest that theophylline induces cyclic AMP signals through PDE inhibition, leading to enhanced gene transcription and subsequent histological changes. (J Toxicol Pathol 2006; 19: 47-52)

show abstract

Beta‐adrenergic receptor mechanisms in rat parotid glands: activation by nerve stimulation and 3‐isobutyl‐1‐methylxanthine.

Cited by 17 publications

References 20 publications

Beta-adrenergic upregulation of the Na(+)-K(+)-2Cl- cotransporter in rat parotid acinar cells.

Beta-adrenergic upregulation of the Na(+)-K(+)-2Cl- cotransporter in rat parotid acinar cells.

Isoproterenol and cAMP Block ERK Phosphorylation and Enhance [Ca2+] Increases and Oxygen Consumption by Muscarinic Receptor Stimulation in Rat Parotid and Submandibular Acinar Cells

Changes in Salivary Gene Expression in F344 Rats Exposed to Theophylline

Contact Info

Product

Resources

About