cAMP Inhibits Transepithelial Chloride Secretion across Bovine Ciliary Body/Epithelium

Wai, Chi; Kong, Chi-Wing; To, Chi‐Ho

doi:10.1167/iovs.03-1343

Cited by 22 publications

(24 citation statements)

References 28 publications

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“…Moreover, gap junctions inhibitors disrupts electrical communications between smooth muscle cells 25) and thus this fact could be blocking the RCs, as observed in other study. 8,14,23) Although heptanol is relatively reliable in blocking gap junctions in a selective mode, 16,17,26,27) 31,32) bovine oocytes, 33) ciliary body 34) and human HeLa cells, 35) heptanol has been either shown 30,32) or assumed 33,34) to act as specific gap junction blocker over a range of concentration (Յ10 mmol/l), substantially larger than those used in our study (0.5 mmol/l). Taken together, the results obtained in this study suggest that heptanol, acting via gap junctions, inhibits the RCs and reveal an important participation of these junctions on oscillations.…”

Section: Discussioncontrasting

confidence: 52%

The Effects of Gap Junction Modulators on the Rhythmic Contractions in Aortas Isolated from Rats Subjected with Sinoaortic Denervation

Rocha

Araújo

Andrade

et al. 2011

Biological & Pharmaceutical Bulletin

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The sinoaortic denervation (SAD) is a proceeding that interrupts the arterial baroreceptor reflex system. The hemodynamic alterations produced by SAD have been extensively studied in many mammals, including rats. There is general agreement that SAD causes a substantial increase in arterial pressure lability with no changes in the mean level of blood pressure.1-3) Therefore, SAD rats can be used to study physiological changes caused by high arterial pressure lability without sustained hypertension. There are few studies analyzing physiological aspects of isolated vessels of SAD rats.Smooth muscle is frequently classified by the manner in which it responds to excitatory stimulation. Therefore, tonic smooth muscle such as that often found in vasculature, airways, gastrointestinal and urogenital systems responds to contractile agonists by producing a simple steady contraction. In contrast, many previous studies have shown that some isolated smooth muscle preparations generate rhythmic contractions (RCs), mainly arterial beds isolated from hypertensive animals. [4][5][6][7][8] Gap junctions are membrane-localized channels which allow intercellular movement of small molecules (relative molecular mass Յ1000), thereby greatly facilitating intercellular communication and coordination of cellular activities.9,10) Gap junctions are blocked by heptanol 10,11) and they can be activated or recruited by tetraethylammonium. 12,13) Gap junctions play a significant role in establishing smooth muscle cell communication in the uterus, which display intense RCs. 14,15) This oscillatory behavior in the uterus is straight associated with an increase in gap junction complex formation between smooth muscle cells.15) Furthermore, inhibitors of gap junctions such as heptanol 16,17) reduce the RCs in the uterus. Isolated rat aortas normally present tonic and stable contractions when stimulated to contract. However, SAD rat aortas present RCs, which are characterized by cycles of fluctuations in tension. 18) In the present study, we also demonstrated an oscillatory behavior in aortas isolated from SAD rats. Additionally, the effect of heptanol and tetraethylammonium (TEA) was investigated in order to explore the role of gap junctional communication on the RCs and supply a pharmacological consideration of the participation of these cellular coupling on vascular reactivity and RCs in aortas from rats with arterial pressure lability evoked by SAD. MATERIALS AND METHODSSinoaortic Denervation All the procedures were carried out in accordance with the Ethical Animal Committee, Ribeirão Preto Campus, University of São Paulo, Brazil. Male Wistar rats (180-210 g) were used throughout the study. Bilateral sinoaortic denervation was performed according to the method reported by Krieger.19) Briefly, the rats were anesthetized with ketamine (50 mg/kg, intraperitoneally (i.p.)) and xylazine (5 mg/kg, i.p.), and suitably fixed in a supine position. An extensive (3-4 cm) middle incision was made into the neck, and the bilateral sternohyoid muscle was rese...

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Section: Discussioncontrasting

confidence: 52%

The Effects of Gap Junction Modulators on the Rhythmic Contractions in Aortas Isolated from Rats Subjected with Sinoaortic Denervation

Rocha

Araújo

Andrade

et al. 2011

Biological & Pharmaceutical Bulletin

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“…Cl -secretion from NPE cells is mediated by Cl -channels, whose activity is controlled by intracellular cyclic adenosine monophosphate (cAMP), which is increased by P2Y 6 receptor activation (51,52). It has been reported that cAMP causes both an increase (52-54) and decrease of Cl -secretion (55)(56)(57). One explanation for these controversial reports might be related to TGFβ-mediated mechanisms.…”

Section: Discussionmentioning

confidence: 99%

“…Because P2Y 6 receptor activation causes TGFβ production (59, 60), UDP may suppress Cl -secretion by producing both TGFβ and cAMP. Another possible candidate is the gap junction because it mediates intercellular connections between PE and NPE cells, which is essential for transepithelial Cl -transport (56,61). Elevation of cAMP caused intercellular uncoupling between PE and NPE cells (56 ]i.…”

Section: Discussionmentioning

confidence: 99%

“…Another possible candidate is the gap junction because it mediates intercellular connections between PE and NPE cells, which is essential for transepithelial Cl -transport (56,61). Elevation of cAMP caused intercellular uncoupling between PE and NPE cells (56 ]i. In addition to NPE cell-mediated mechanisms, P2Y 6 receptors are localized in the stroma of the ciliary process (16).…”

Section: Discussionmentioning

confidence: 99%

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Purinergic dysregulation causes hypertensive glaucoma–like optic neuropathy

Shinozaki¹,

Kashiwagi²,

Namekata³

et al. 2017

JCI Insight

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“…However, in a recent detailed characterization of its effects on vascular smooth muscle cells (Matchkov et al, 2004), it was shown that heptanol, over the range of concentrations used in our study (0.5-2.0 mM), potently increased the input resistance of the cells and desynchronized their [Ca 2+ ]i oscillations, indicating that it powerfully uncoupled the cells. Indeed, in several recent studies carried out on a range of cell / tissue preparations, including mouse heart (Knapp et al, 2005), rabbit heart (Przyklenk et al, 2005), bovine oocytes (Atef et al, 2005), ciliary body (Do et al, 2004), and human HeLa cells (Bader and Weingart, 2004), heptanol has been either shown (Knapp et al, 2005;Atef et al, 2005) or assumed (Do et al, 2004;Bader and Weingart, 2004) to act as a specific gap junction blocker over a range of concentrations (≤ 10 mM), substantially larger than those used in our study (≤ 2 mM). In our own studies on mammalian vas deferens, the concentrations of heptanol employed to study the effects of uncoupling have not been found to affect resting potential (guinea-pig vas deferens: Manchanda and Venkateswarlu, 1997; rat vas deferens: Palani and Manchanda, unpublished observations), indicating a lack of effect on membrane ion channels.…”

Section: Role Of Cell-to-cell Coupling In Na-induced Contractionmentioning

confidence: 66%

Effect of heptanol on noradrenaline-induced contractions in rat vas deferens

Palani

Manchanda

2006

J. Smooth Muscle Res.

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We have studied the effects of 1-heptanol and nifedipine on noradrenaline (NA)-induced contractions in order to explore the role of gap junctions and their interactions with L-type Ca 2+ channel mediated [Ca 2+ ]o entry in the generation of NA-induced contractions in the rat vas deferens. Application of 20 μM NA to rat vas deferens resulted in contractions with three different components, an initial phasic component followed by a tonic component overlapped with an oscillatory component. Heptanol (0.01-2 mM) induced a concentration dependent reduction of the contractions. 2 mM heptanol reduced the phasic component by 32.9 ± 4.4% and the tonic component by 93.8 ± 1.9% of control, while the oscillatory component was completely abolished (n=7). Nifedipine (2 μM) reduced the phasic component by 34.5 ± 4.1% and the tonic component by 89.5 ± 3.8% of control and abolished the oscillatory component (n=6). In the presence of heptanol and nifedipine together, the phasic component was reduced by 61.3 ± 8.3% and the tonic component by 94.5 ± 1.0% of control. The oscillatory component was completely abolished (n=6). These results allow the conclusion that phasic contraction is mainly due to the direct action of NA, independent of gap junctions, while the tonic and oscillatory contractions may depend significantly on cell-to-cell communication. These in turn may depend critically on the availability of extracellularly derived Ca 2+ .

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cAMP Inhibits Transepithelial Chloride Secretion across Bovine Ciliary Body/Epithelium

Abstract: The results suggest that cAMP plays a crucial role in modulating Cl(-) secretion across the ciliary epithelium. The effect is possibly mediated, at least in part, by the regulation of the permeability of gap junctions between pigmented and nonpigmented ciliary epithelial cells.

Cited by 22 publications

References 28 publications

The Effects of Gap Junction Modulators on the Rhythmic Contractions in Aortas Isolated from Rats Subjected with Sinoaortic Denervation

The Effects of Gap Junction Modulators on the Rhythmic Contractions in Aortas Isolated from Rats Subjected with Sinoaortic Denervation

Purinergic dysregulation causes hypertensive glaucoma–like optic neuropathy

Effect of heptanol on noradrenaline-induced contractions in rat vas deferens

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