Pre-junctional inhibitory action of prostaglandin E2 on excitatory neuro-effector transmission in the human bronchus

Ito, Isao; Suzuki, Hiroyoshi; Aizawa, Hisamichi; Hirose, Takahito; Hakoda, Hiroyuki

doi:10.1016/0090-6980(90)90024-p

Cited by 34 publications

(13 citation statements)

References 25 publications

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“…PGE 2 (23,36,52,56,59,74) and the structurally related E-ring 8-isoprostanes, resulting from lipid peroxidation, have been shown to inhibit release of ACh from cholinergic neurons in airway smooth muscle preparations, whereas the opposite effect has been reported in guinea pig ileal preparations (15,38,50). The difference in the effects of PGE 2 may be related to different prostaglandin E receptor subtypes present in the different preparations.…”

Section: Discussionmentioning

confidence: 88%

Platelet-activating factor and prostaglandin E₂impair esophageal ACh release in experimental esophagitis

Cheng

Cao

Fiocchi³

et al. 2005

American Journal of Physiology-Gastrointestinal and Liver Physi

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ACh is a neurotransmitter in cat esophageal circular muscle, as atropine nearly abolishes contraction of in vitro circular muscle strips in response to electric field stimulation (EFS) (5, 12). Experimental esophagitis reduced EFS- but not ACh-induced contraction of esophageal circular muscle, suggesting that esophagitis impairs neurotransmitter release. Because IL-1beta and IL-6 are produced in esophagitis and reproduce these changes in normal esophageal muscle (12), we examined the role of IL-1beta and IL-6 in this motor dysfunction. IL-1beta, IL-6 (12), H2O2, PGE2, and platelet-activating factor (PAF) were elevated in esophagitis specimens. Normal muscle incubated (2 h) in IL-1beta and IL-6 had increases in H2O2, PGE2, and PAF levels. H2O2 contributed to increased PGE2 and PAF, as the increase was partially (60-80%) reversed by the H2O2 scavenger catalase. EFS-induced [3H]ACh release from muscle strips significantly (42%) decreased in esophagitis and after 2 h incubation in PGE2 and in PAF C-16. Similarly, EFS-induced but not ACh-induced muscle contraction decreased in esophagitis and after incubation in PGE2 and PAF C-16. Finally, in normal muscle strips treated with IL-1beta electrical field stimulation (EFS)-induced contraction was partially restored by indomethacin or by the PAF antagonist CV3988 and was completely restored by the combination of CV3988 and indomethacin, whereas in strips treated with IL-6, EFS-induced contraction was partially restored by the PAF antagonist CV3988 and not affected by indomethacin. We conclude that IL-1beta-induced production of H2O2 causes formation of PGE2 and PAF that inhibit ACh release from esophageal cholinergic neurons without affecting ACh-induced contraction of esophageal circular muscle. IL-6 causes production of H2O2, PAF, and other unidentified inflammatory mediators.

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Section: Discussionmentioning

confidence: 88%

Platelet-activating factor and prostaglandin E₂impair esophageal ACh release in experimental esophagitis

Cheng

Cao

Fiocchi³

et al. 2005

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Proinflammatory mediators such as histamine and bradykinin have also been shown to stimulate PGE2 production from canine tracheal strips (Anderson et al, 1980) and in human cultured tracheal epithelial cells (Churchill et al, 1989) respectively. Any PGE2 release by these mediators might feed back to inhibit inflammatory cell function (Giembycz et al, 1990;Christman & Christman, 1990;Minakuchi et al, 1990) and acetylcholine release from cholinergic nerve terminals (Ito et al, 1990), thus suggesting a novel role for airway smooth muscle and airway epithelium in producing an anti-inflammatory mediator which may exert a braking effect on the inflammatory process. The protective effects of PGE2 are likely to be due to its anti-inflammatory effects rather than effects on smooth muscle as its effects on airway smooth muscle are weak and variable in vitro (Sweatman & Collier, 1968).…”

Section: Discussionmentioning

confidence: 99%

“…In vitro, PGE2 inhibits acetylcholine release from parasympathetic nerve endings in human airway smooth muscle (Ito et al, 1990). It inhibits release of mediators from human lung mast cells (Peters et al, 1982) and inhibits cellular responses in other inflammatory cells such as eosinophils (Giembycz et al, 1990), macrophages (Christman & Christman, 1990) and T-lymphocytes (Minakuchi et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

Production of PGE₂ by bovine cultured airway smooth muscle cells and its inhibition by cyclo‐oxygenase inhibitors

Delamere

Holland

Patel

et al. 1994

British J Pharmacology

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1 Prostaglandin E2 (PGE2) is thought to be an important inhibitory modulator of inflammatory processes in the airway. It inhibits inflammatory cell function and cholinergic neurotransmission in vitro and roles have been postulated in vivo in refractoriness and in the mechanism of action of the diuretic agent, frusemide. 2 The production of PGE2 by bovine cultured airway smooth muscle cells has been studied under a range of conditions. The effects of cyclo-oxygenase inhibitors (flurbiprofen, indomethacin, acetyl salicylic acid) on serum-induced production of PGE2 were assessed over a range of concentrations (10-7-I04 M).3 Serum-stimulated production of PGE2 in control wells ranged from 350 to 800 ng PGE2 ml-' in cells from different animals. All three cyclo-oxygenase inhibitors inhibited PGE2 production with an order of potency, flurbiprofen > indomethacin > acetyl salicylic acid. Log IC50 values were -6.24 for flurbiprofen, -5.23 for indomethacin and -3.50 for acetyl salicylic acid. 4 PGE2 production was stimulated by arachidonic acid (10-5 M) or addition of the proinflammatory mediator, bradykinin (108--105 M). 5 Incubation of cells for 24 h with 5 bromo deoxyuridine (BRDU) (10-4 M) to prevent DNA synthesis did not alter PGE2 production in response to serum, suggesting that it was not a function of proliferation per se. 6 Our study suggests that airway smooth muscle may be an important source of PGE2. Production of PGE2 may be a novel feedback mechanism whereby airway smooth muscle cells can negatively modulate airways inflammation. The differing potencies of the cyclo-oxygenase inhibitors may explain the contrasting effect of these drugs in recent studies in asthma.

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“…Under different circumstances COX products may have a protective role. PGE 2 has been shown to have a potential bronchoprotective role both in vitro [6,7] and in vivo [8,9]. Studies showing that oral indomethacin inhibits refractoriness to repeated bronchoconstriction challenge suggest that endogenous PGE 2 may be involved in this protective response [10,11].…”

mentioning

confidence: 99%

Selectivity of cyclo-oxygenase inhibitors in human pulmonary epithelial and smooth muscle cells

Range¹,

Pang²,

Holland³

et al. 2000

Eur Respir J

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Selectivity of cyclo-oxygenase inhibitors in human pulmonary epithelial and smooth muscle cells. S.P. Range, L. Pang, E. Holland, A.J. Knox. #ERS Journals Ltd 2000. ABSTRACT: Cyclo-oxygenase (COX) inhibitors may have a role in reducing inflammation in asthma and other pulmonary diseases. COX inhibitors have different selectivities for the two COX isoenzymes (COX 1 and COX 2) which vary between purified enzyme and intact cell preparations. The relative selectivity of COX inhibitors has not been studied in human airway cells.A number of COX inhibitors in cultured human airway cells were compared which exclusively express either COX 1 (primary degree cultured human airway smooth muscle (HASM) cells) or COX 2 (A549 pulmonary epithelial cell-line) as measured by Western blotting. COX activity was assayed by prostaglandin (PG)E 2 production following 30 min incubation with 5 mM arachidonic acid.COX activity in both cell types was similar; HASM cells 92. -5 M for aspirin. Sodium valerate had no effect in either HASM or A549 cells. The COX 2:COX 1 selectivity ratio (COX 2 IC50/COX 1 IC50) was <0.0001 for nimesulide, 0.001 for NS398, 0.03 for flurbiprofen and 1.9 for indomethacin.In conclusion the present study has shown that cyclo-oxygenase inhibitors have a range of selectivities for cyclo-oxygenase 1 and cyclo-oxygenase 2 in intact human airway cells. The relative cyclo-oxygenase 2 selectivity of N-(2-cyclohexyloxy-4-nitrophenyl)-methanesulphonamide and nimesulide may have implications for the treatment of asthma and other inflammatory pulmonary diseases. Recent studies have suggested that cyclo-oxygenase (COX) products may be involved in the pathophysiology of several pulmonary diseases: COX products have been implicated in the inflammation found in asthmatic airways, with different COX products exerting differential effects in different situations in vivo [1±3]. Inhaled indomethacin and aspirin protect against indirect bronchoconstrictor challenges in asthma [4,5] suggesting that release of constrictor prostaglandins such as prostaglandin (PG)D 2 and PGF 2a may contribute to the mechanisms of action of these stimuli. Under different circumstances COX products may have a protective role. PGE 2 has been shown to have a potential bronchoprotective role both in vitro [6,7] and in vivo [8,9]. Studies showing that oral indomethacin inhibits refractoriness to repeated bronchoconstriction challenge suggest that endogenous PGE 2 may be involved in this protective response [10,11]. A small number of patients with asthma exhibit aspirin sensitivity, whereby oral aspirin and other COX inhibitors produce bronchochoconstriction. This bronchoconstriction can be prevented by inhalation of PGE 2 [12,13]. Collectively these studies implicate COX products in several aspects of asthma pathophysiology, but it is clear that the responses to COX inhibition depend on the inhibitor studied, the route of administration, the circumstances of use and the type of patients studied. Studies in cultured airway smooth muscle cells in vitro have sug...

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Pre-junctional inhibitory action of prostaglandin E2 on excitatory neuro-effector transmission in the human bronchus

Cited by 34 publications

References 25 publications

Platelet-activating factor and prostaglandin E₂impair esophageal ACh release in experimental esophagitis

Platelet-activating factor and prostaglandin E₂impair esophageal ACh release in experimental esophagitis

Production of PGE₂ by bovine cultured airway smooth muscle cells and its inhibition by cyclo‐oxygenase inhibitors

Selectivity of cyclo-oxygenase inhibitors in human pulmonary epithelial and smooth muscle cells

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Pre-junctional inhibitory action of prostaglandin E2 on excitatory neuro-effector transmission in the human bronchus

Cited by 34 publications

References 25 publications

Platelet-activating factor and prostaglandin E2impair esophageal ACh release in experimental esophagitis

Platelet-activating factor and prostaglandin E2impair esophageal ACh release in experimental esophagitis

Production of PGE2 by bovine cultured airway smooth muscle cells and its inhibition by cyclo‐oxygenase inhibitors

Selectivity of cyclo-oxygenase inhibitors in human pulmonary epithelial and smooth muscle cells

Contact Info

Product

Resources

About

Platelet-activating factor and prostaglandin E₂impair esophageal ACh release in experimental esophagitis

Platelet-activating factor and prostaglandin E₂impair esophageal ACh release in experimental esophagitis

Production of PGE₂ by bovine cultured airway smooth muscle cells and its inhibition by cyclo‐oxygenase inhibitors