Characterization of the prostaglandin E<sub>2</sub> sensitive (EP)‐receptor in the rat isolated trachea

Lydford, S.J.; McKechnie, K.

doi:10.1111/j.1476-5381.1994.tb13042.x

Cited by 26 publications

(27 citation statements)

References 15 publications

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“…FINNEY and co-workers [158,267] have reported that long-term systemic treatment of rats with salbutamol and salmeterol blocks the ability of these agonists subsequently to protect against acetylcholine-induced bronchoconstriction. Moreover, the bronchoprotective effect of PGE 2 , which also acts through Gs-coupled prostanoid receptors of the PGE 2 receptor 4 subtype in rat airways [269], was similarly abolished, indicating that a state of heterologous desensitisation had been effected. Significantly, further studies found that, in the lungs of rats treated with b 2 -adrenoceptor agonists, there was a ,50% reduction in the level of Gsa and an associated impaired ability of cholera toxin to promote cAMP accumulation ex vivo.…”

Section: Downregulation Of Stimulatory G-protein Subunit Amentioning

confidence: 80%

Beyond the dogma: novel β₂-adrenoceptor signalling in the airways

Giembycz

Newton²

2006

Eur Respir J

132

118

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b 2 -Adrenoceptor agonists evoke rapid bronchodilatation and are the mainstay of the treatment of asthma symptoms worldwide. The mechanism of action of this class of compounds is believed to involve the stimulation of adenylyl cyclase and subsequent activation of the cyclic adenosine monosphosphate (cAMP)/cAMP-dependent protein kinase cascade.This classical model of b 2 -adrenoceptor-mediated signal transduction is deeply entrenched, but there is compelling evidence that agonism of b 2 -adrenoceptors can lead to the activation of multiple effector pathways, which now compels researchers in academia and the pharmaceutical industry alike to think beyond the traditional dogma. Therefore, the regulation by b 2 -adrenoceptor agonists of responses, including airways smooth muscle tone and the secretory capacity of the epithelium and pro-inflammatory/immune cells, may be highly complex, involving both cAMPdependent and -independent mechanisms that, in many cases, may act in concert.In this article, the current status of b 2 -adrenoceptor-mediated signalling in the airways is reviewed in the context of understanding mechanisms that may underlie both the beneficial and detrimental effects of these drugs in asthma symptom management.

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Section: Downregulation Of Stimulatory G-protein Subunit Amentioning

confidence: 80%

Beyond the dogma: novel β₂-adrenoceptor signalling in the airways

Giembycz

Newton²

2006

Eur Respir J

132

118

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“…Albuterol-induced desensitization was studied in more detail by examining the effect of PGE 2 , which relaxes rat airways by stimulating adenylyl cyclase through EP 4 -like prostanoid receptors (31). The demonstration that the antispasmogenic activity of PGE 2 was also impaired indicates that the desensitization was heterologous.…”

Section: Discussionmentioning

confidence: 99%

Albuterol-induced downregulation of Gsα accounts for pulmonary β2-adrenoceptor desensitization in vivo

Finney

Belvisi²,

Donnelly³

et al. 2000

J. Clin. Invest.

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Figure 2Effect of chronic treatment of rats with albuterol (a-d) or PGE 2 (e and f) on lung function in anesthetized rats. Animals were given albuterol, PGE 2 (open bars; both 40 µg/kg/h) or vehicle (filled bars) for 7 days and then instrumented for the measurement of lung function. ACh (500 µg/kg intravenously) was administered and the maximum increase in overflow pressure was measured. When baseline lung function was reestablished, albuterol (Alb; 100 µg/kg; a and f), PGE 2 (PG; 300 µg/kg; b and e), forskolin (F; 300 µg/kg; c), or IBMX (300 µg/kg; d) was given intravenously, and 5 minutes later, ACh was administered again and any change in overflow pressure was noted. Each bar represents the mean ± SEM of four independent determinations. A P < 0.05, significant protection of ACh-induced bronchoconstriction.

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“…In particular, together with the EP2 receptor, EP4 transcripts and proteins are abundantly expressed in human airway smooth muscle cells (Bradbury et al, 2005;Clarke et al, 2005;Mori et al, 2011;Benyahia et al, 2012). It is also known that EP4 activation causes potent relaxation in human and rat bronchial preparations (Lydford and McKechnie, 1994;Benyahia et al, 2012).…”

Section: +mentioning

confidence: 99%