β‐Adrenoceptors mediate inhibition of [<sup>3</sup>H]‐acetylcholine release from the isolated rat and guinea‐pig trachea: role of the airway mucosa and prostaglandins

Wessler, Ignaz; Reinheimer, Torsten; Brunn, Gernot; Anderson, Gary P.; Maclagan, Jennifer; Racké, Kurt

doi:10.1111/j.1476-5381.1994.tb17128.x

Cited by 33 publications

(15 citation statements)

References 31 publications

(49 reference statements)

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“…In particular, Wessler et al' (1994) found that isoprenaline inhibited, rather than enhanced, the EFS-induced output of ACh from parasympathetic nerves that innervate both guinea-pig and rat airways. Significantly, however, the inhibition of neurotransmitter output by isoprenaline was not apparent in epithelium-denuded preparations or when cyclo-oxygenase was inhibited (Wessler et al, 1994). Since JJ-adrenoceptor agonists enhance phospholipase A2 activity in guinea-pig lung (Blackwell et al, 1978;Suzuki et al, 1987) and generate PGD2 and PGE2 from airway epithelial cells, Wessler et al (1994) concluded that stimulation of,Badrenoceptors on airway epithelial cells leads to the liberation of prostanoids which then act to inhibit EFS-evoked ACh release.…”

Section: Discussionmentioning

confidence: 99%

“…The trachea was dissected away from the lungs and main bronchi and opened longitudinally by cutting through the cartilage; the epithelium was subsequently removed by careful dissection, minimizing damage to the smooth muscle. Indomethacin (10 pM) was present throughout to prevent the formation of endogenous prostaglandins which are known to affect cholinergic neurotransmission and ACh release per se (Walters et al, 1984;Deckers et al, 1989;Wessler et al, 1994).…”

Section: Methodsmentioning

confidence: 99%

“…In some studies, this problem has been circumvented by measuring directly the output of ACh following EFS of the parasympathetic supply. In canine trachea, for example, noradrenaline has no effect on ACh release evoked by electrical field stimulation (Martin & Collier, 1986) whereas more recent experiments have demonstrated that activation of pre-junctional j3-adrenoceptors inhibits cholinergic neurotransmission in rat and guinea-pig airways (Wessler et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

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Paradoxical facilitation of acetylcholine release from parasympathetic nerves innervating guinea‐pig trachea by isoprenaline

Belvisi

Patel

Takahashi

et al. 1996

British J Pharmacology

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1 Previous studies have provided evidence that activation of fl-adrenoceptors on cholinergic nerve terminals can inhibit neurotransmission in the airways. However, in most cases, this conclusion has been based on indirect evidence obtained from mechanical experiments where changes in airways smooth muscle tone were measured.2 We have assessed whether modulation of cholinergic neurotransmission by fl-adrenoceptor agonists is due to a pre-or post-junctional action by investigating the effect of isoprenaline on contractile responses evoked by exogenous acetylcholine (ACh) and electrical field stimulation (EFS; 4 Hz, 40 V, 0.5 ms pulse width every 15 s), and on EFS-induced ACh release from cholinergic nerves innervating guinea-pig and human trachea. Furthermore, the subtype of /3-adrenoceptor which modulates neurotransmission and the potential role of cyclic AMP in this response were evaluated. 3 In guinea-pig trachea, isoprenaline (1 nM-1 -IM) inhibited the contractile response evoked by exogenous ACh (1 gM) to a similar extent to that evoked by EFS (EC50 = 19.9 and 23 nM, respectively). 4 In epithelium-denuded guinea-pig strips treated with indomethacin (10 gM), isoprenaline significantly enhanced EFS-induced ACh release from cholinergic nerve terminals (by 36% at 0.3 gM). This effect was blocked by propranolol and ICI 118, 551 (each 0.1 gM). In contrast, isoprenaline failed to affect EFSinduced ACh release from parasympathetic nerves innervating human trachea. 5 To evaluate the role of cyclic AMP in the /3-adrenoceptor-induced facilitation of cholinergic neurotransmission, the effects of various cyclic AMP elevating drugs on ACh release were studied.Forskolin (10 gM) significantly augmented (by 17%) EFS-induced ACh release, an effect which was not reproduced by 1,9-dideoxyforskolin (10 gM) which does not activate adenylyl cyclase. Similarly, the cyclic AMP analogue, 8-bromo-cyclic AMP (1 mM) and cholera toxin (1 Mg ml-') facilitated ACh output by 22 and 47% respectively, whereas prostaglandin E2 (PGE2, 0.1 nM-I gM) inhibited this response (by 67% at 1 Mm).6 Zardaverine (10 gM), a dual inhibitor of the phosphodiesterase (PDE)3 and PDE4 isoenzyme families, did not affect EFS-induced ACh release and failed to facilitate the actions of either isoprenaline or PGE2. Similarly, neither SK&F 94120 (10 uM) nor rolipram (10 gM), selective inhibitors of PDE3 and PDE4 respectively, significantly affected the release of ACh in response to EFS. 7 The result of this study suggests that isoprenaline facilitates cholinergic neurotransmission in guineapig, but not human, trachea by activation of pre-junctional /32-adrenoceptors, an effect that may be mediated via activation of the cyclic AMP/cyclic AMP-dependent protein kinase cascade. Furthermore, the data presented herein illustrate the need to undertake direct measurements of neurotransmitter release when examining the effect of agents purported to act pre-junctionally.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Paradoxical facilitation of acetylcholine release from parasympathetic nerves innervating guinea‐pig trachea by isoprenaline

Belvisi

Patel

Takahashi

et al. 1996

British J Pharmacology

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“…The binding of Sal to the β 2 receptor induces activation of adenylate cyclase and consequently cAMP generation that eventually leads to a reduction of cytosolic calcium availability resulting in smooth muscle relaxation [16]. A second mechanism of action for these β 2 agonist drugs involving the stimulation of prejunctional receptors of the human [17] and guinea pig trachea nerves [18] has been described.This prejunctional stimulation causes inhibition of the cholinergic-mediated airway smooth muscle contractionand may be an important mechanism by which β 2 agonists induce airway smooth muscle relaxation. A possible third mechanism of action has been described for the relaxant actions of β 2 adrenoceptors in the airways.…”

Section: Introductionmentioning

confidence: 99%

“…A possible third mechanism of action has been described for the relaxant actions of β 2 adrenoceptors in the airways. The mechanism proposes an interaction between NO availability and the action of B 2 agonists mediated via the non-adrenergic non-cholinergic neural pathways [18]. …”

Section: Introductionmentioning

confidence: 99%

Nitric Oxide Is Involved in the Response of the Isolated Intact and Epithelium-Denuded Rat Trachea to the β<sub>2</sub> Adrenergic Receptor Agonist Salbutamol

Montalvo

Cantres-Fonseca²,

Santos³

et al. 2010

Respiration

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Background: The involvement of the airway smooth muscle mediator nitric oxide (NO) in the actions of the β₂ agonist salbutamol (Sal), a well- known bronchodilator, is very poorly understood. Objectives: To determine if endogenous NO release is a major factor in the Sal-induced relaxation of the carbachol- and electrical field-stimulated rat trachea and determine the role of the tracheal epithelium as the possible source of NO involved in these effects. Methods: Isolated carbachol- or electric field-stimulated pre-contracted in vitro male Sprague Dawley rat tracheas (with epithelium intact or denuded) were relaxed with incremental or discrete concentrations of Sal in the presence and absence of the NO synthesis inhibitor L-NAME. Results: Epithelium-denuded tracheas showed a reduced relaxation response to Sal. L-NAME (1 mM) similarly decreased the sensitivity of the rat tracheas to Sal in both epithelium-intact and -denuded conditions. In the presence of L-NAME, high concentrations of Sal induced an unexpectedly large relaxation response in carbachol-stimulated rat tracheas with both intact and denuded epithelium. Sal relaxation was also affected by L-NAME in electrical field-stimulated epithelium-intact and -denuded tracheas. Conclusion: The results suggest that NO derived from sources other than the epithelium is an important mediator of the Sal-induced relaxation in rat tracheas.

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Cholinergic and noncholinergic parasympathetic control of airway smooth muscle

Undem

Myers

2001

Muscarinic Receptors in Airways Diseases

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β‐Adrenoceptors mediate inhibition of [³H]‐acetylcholine release from the isolated rat and guinea‐pig trachea: role of the airway mucosa and prostaglandins

Cited by 33 publications

References 31 publications

Paradoxical facilitation of acetylcholine release from parasympathetic nerves innervating guinea‐pig trachea by isoprenaline

Paradoxical facilitation of acetylcholine release from parasympathetic nerves innervating guinea‐pig trachea by isoprenaline

Nitric Oxide Is Involved in the Response of the Isolated Intact and Epithelium-Denuded Rat Trachea to the β<sub>2</sub> Adrenergic Receptor Agonist Salbutamol

Cholinergic and noncholinergic parasympathetic control of airway smooth muscle

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β‐Adrenoceptors mediate inhibition of [3H]‐acetylcholine release from the isolated rat and guinea‐pig trachea: role of the airway mucosa and prostaglandins

Cited by 33 publications

References 31 publications

Paradoxical facilitation of acetylcholine release from parasympathetic nerves innervating guinea‐pig trachea by isoprenaline

Paradoxical facilitation of acetylcholine release from parasympathetic nerves innervating guinea‐pig trachea by isoprenaline

Nitric Oxide Is Involved in the Response of the Isolated Intact and Epithelium-Denuded Rat Trachea to the β<sub>2</sub> Adrenergic Receptor Agonist Salbutamol

Cholinergic and noncholinergic parasympathetic control of airway smooth muscle

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β‐Adrenoceptors mediate inhibition of [³H]‐acetylcholine release from the isolated rat and guinea‐pig trachea: role of the airway mucosa and prostaglandins