Ethanol increases phosphodiesterase 4 activity in bovine bronchial epithelial cells

Forgèt, Mary A.; Sisson, Joseph H.; Spurzem, John R.; Wyatt, Todd A.

doi:10.1016/j.alcohol.2003.06.005

Cited by 21 publications

(23 citation statements)

References 16 publications

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“…This observation supports our in vitro cellular studies of intact ciliated epithelial CBF desensitization to isoproterenol after chronic ethanol exposure (Wyatt and Sisson, 2001). Results from similar in vitro studies have shown that the ethanol desensitization response is not exclusively regulated at the level of the β-adrenergic receptors (Wyatt and Sisson, 2001), phosphodiesterase activation (Forgèt et al, 2003), or proinflammatory cytokine production (Allen-Gipson et al, 2004). Instead, ethanol appears to acutely stimulate CBF via nitric oxide (Sisson, 1995) and cAMP-dependent (Sisson et al, 1999) pathways.…”

Section: Discussionsupporting

confidence: 76%

“…This follows the observation that either cAMP or cyclic guanosine monophosphate (cGMP) elevations result in increased cilia beating (Wyatt et al, 1998). However, continued exposure to ethanol eventually results in a return to baseline, unstimulated levels of cilia beating as potentially mediated via the action of a cAMP-phosphodiesterase (Forgèt et al, 2003). Once ciliated cells have been chronically exposed to ethanol in this manner, repeat challenges with ethanol fail to stimulate ciliary motility increase.…”

mentioning

confidence: 99%

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Desensitization of PKA‐Stimulated Ciliary Beat Frequency in an Ethanol‐Fed Rat Model of Cigarette Smoke Exposure

Wyatt

Gentry-Nielsen

Pavlik

et al. 2004

Alcoholism Clin & Exp Res

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Background-Our previous studies have shown that the ciliary beat frequency (CBF) of cultured ciliated airway epithelial cells exposed to chronic ethanol fails to increase in response to β-agonist stimulation. This loss of the ciliary "flight response" correlates with an ethanol-mediated desensitization of adenosine 3':5'-cyclic monophosphate-dependent protein kinase (PKA), a known regulatory component of CBF stimulation. We hypothesized that a similar ethanol-mediated desensitization of CBF would occur in vivo.

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Section: Discussionsupporting

confidence: 76%

mentioning

confidence: 99%

Desensitization of PKA‐Stimulated Ciliary Beat Frequency in an Ethanol‐Fed Rat Model of Cigarette Smoke Exposure

Wyatt

Gentry-Nielsen

Pavlik

et al. 2004

Alcoholism Clin & Exp Res

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“…Novelty seeking or exploratory behaviors appear positively associated with ethanol intake or drug use (Davis et al 2008; Nadal et al 2002), although there are different observations (Bienkowski et al 2001; Kliethermes et al 2007). Furthermore, chronic ethanol exposure increases LPS-inducible expression of PDE4B in monocytes/macrophages (Gobejishvili et al 2008); incubation of bovine bronchial epithelial cells with ethanol increases PDE4 activity (Forget et al 2003). Further studies using mice deficient in PDE4B will help identify the role of PDE4B in the regulation of ethanol intake.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of phosphodiesterase-4 decreases ethanol intake in mice

Chen

et al. 2011

Psychopharmacology

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Rationale Cyclic AMP (cAMP)-protein kinase A (PKA) signaling has been implicated in the regulation of ethanol consumption. Phosphodiesterase-4 (PDE4) specifically hydrolyzes cAMP and plays a critical role in controlling intracellular cAMP levels in the brain. However, the role of PDE4 in ethanol consumption remains unknown. Objective To examine whether PDE4 was involved in regulating ethanol intake. Methods The two-bottle choice paradigm was used to assess intake of ethanol, sucrose, and quinine in C57BL/6J mice treated with the selective PDE4 inhibitor rolipram or Ro 20-1724; locomotor activity was also monitored using the open-field test in mice treated with rolipram. Results Administration (i.p.) of either rolipram (0.25 and 0.5 mg/kg) or Ro 20-1724 (10 mg/kg) reduced ethanol intake and preference by 60-80%, but did not alter total fluid intake. In contrast, rolipram even at the higher dose of 0.5 mg/kg was not able to affect intake of sucrose or quinine, alcohol-induced sedation, or blood ethanol elimination. At 0.5 mg/kg, rolipram did decrease locomotor activity, but the effect only lasted for approximately 40 min, which did not likely affect behavior of ethanol drinking. Conclusions These results suggest that PDE4 is a novel target for drugs that reduce ethanol intake; PDE4 inhibitors may be used for treatment of alcohol dependence.

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“…Unlike primary cultures of rat hepatocytes, where a rapid decline in CYP2E1 mRNA prevents further accumulation of CYP2E1, the synthesis of CYP2E1 persists in whole animals. Furthermore, ethanol has been shown to stimulate adenylate cyclase and cAMP-dependent PKA activity [35,36]. This might increase the targeting of CYP2E1 to mitochondria which is activated by the cAMPdependent, PKA-mediated phosphorylation of Ser-129 [16].…”

Section: Treatmentmentioning

confidence: 99%

Ethanol increases mitochondrial cytochrome P450 2E1 in mouse liver and rat hepatocytes

Robin

Grandperret

et al. 2005

FEBS Letters

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Enhanced hepatic levels of cytochrome P450 2E1 (CYP2E1) may play a key role in the pathogenesis of some liver diseases because CYP2E1 represents a significant source of reactive oxygen species. Although a large fraction of CYP2E1 is located in the endoplasmic reticulum, CYP2E1 is also present in mitochondria. In this study, we asked whether ethanol, a known inducer of microsomal CYP2E1, could also increase CYP2E1 within mitochondria. Our findings indicated that ethanol increased microsomal and mitochondrial CYP2E1 in cultured rat hepatocytes and in the liver of lean mice. This was associated with decreased levels of glutathione, possibly reflecting increased oxidative stress. In contrast, in leptin-deficient obese mice, ethanol administration did not increase mitochondrial CYP2E1, nor it depleted mitochondrial glutathione, suggesting that leptin deficiency hampers mitochondrial targeting of CYP2E1. Thus, ethanol intoxication increases CYP2E1 not only in the endoplasmic reticulum but also in mitochondria, thus favouring oxidative stress in these compartments.

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Ethanol increases phosphodiesterase 4 activity in bovine bronchial epithelial cells

Cited by 21 publications

References 16 publications

Desensitization of PKA‐Stimulated Ciliary Beat Frequency in an Ethanol‐Fed Rat Model of Cigarette Smoke Exposure

Desensitization of PKA‐Stimulated Ciliary Beat Frequency in an Ethanol‐Fed Rat Model of Cigarette Smoke Exposure

Inhibition of phosphodiesterase-4 decreases ethanol intake in mice

Ethanol increases mitochondrial cytochrome P450 2E1 in mouse liver and rat hepatocytes

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