Influence of the epithelium on acetylcholine release from parasympathetic nerves of the rat trachea

Vlahos, Ross; Fabiani, Maurice E.; Story, D. F.

doi:10.1046/j.1365-2680.2000.00187.x

Cited by 3 publications

(1 citation statement)

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“…These receptors which are known to inhibit or facilitate the release of acetylcholine have also been localized in nonneuronal tissues including the tracheal epithelium (Vlahos et al, 2000). In epitheliumintact tracheal preparations, acetylcholine efflux was enhanced in the presence of the muscarinic antagonist, atropine raising the possibility that the increased release of acetylcholine was due to blockade of prejunctional muscarinic autoreceptors on nerve terminals.…”

Section: Discussionmentioning

confidence: 99%

Non-neuronal acetylcholine and urinary bladder urothelium

et al. 2007

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Non-neuronal release of acetylcholine (ACh) has been proposed to play a role in urinary bladder function. These studies investigated the expression and function of the non-neuronal cholinergic system in cultured urothelial cells isolated from the rat urinary bladder. Our findings have revealed that urothelial cells express the high-affinity choline transporter (CHT1) and acetylcholine synthesizing enzymes, choline acetyltransferase (ChAT) and carnitine acetyltransferase (CarAT). In contrast to neurons, urothelial cells do not express the vesicular acetylcholine transporter (VAChT) but do express OCT3, a subtype of polyspecific organic cation transporter (OCT) that is thought to be involved in the release of acetylcholine from nonneuronal cells. Following exposure of cultured urothelial cells to 3 H-choline, radioactivity was detected in the cells and increased release of radioactivity into the eternal media was evoked by mechanical stimulation (exposure of the cells to 50% hypotonic Krebs) or chemical stimulation of purinergic receptors by 100 μM ATP. The present experiments did not establish if the evoked release of radioactivity (termed 3 HACh release in this paper) was due to release of acetylcholine or choline. 3 H-ACh release was not evoked by application of acetylcholine alone, however pretreatment with the non-selective muscarinic receptor antagonist atropine prior to application of acetylcholine facilitated 3 H-ACh release, suggesting that the acetylcholine released from urothelial cells may participate in a negative feedback mechanism by acting on muscarinic receptors to inhibit its own release in the urothelium. Brefeldin, an agent which disrupts vesicular exocytosis, did not block hypotonicevoked 3 H-ACh release. These observations indicate that acetylcholine release from urothelial cells is mediated by different mechanisms than those such as vesicular storage and exocytosis that underlie the release of neurotransmitters from nerves.

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Section: Discussionmentioning

confidence: 99%

Non-neuronal acetylcholine and urinary bladder urothelium

et al. 2007

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Cromakalim inhibits transmitter acetylcholine release in rat trachea by an action on epithelial cells and a diffusible factor

Vlahos

Fabiani

Story

2003

Naunyn-Schmiedeberg's Archives of Pharmacology

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The present study was undertaken to investigate further the effects of the potassium channel opening drug cromakalim on the release of transmitter acetylcholine from cholinergic nerves of rat isolated trachea by using two tracheal preparations superfused in series. In all experiments, the lower chamber contained an epithelium-denuded preparation which had been incubated with [3H]-choline to incorporate [3H]-acetylcholine into cholinergic transmitter stores, whereas the upper chamber contained an unlabelled, epithelium-intact or epithelium-denuded preparation. When the upper chamber contained an epithelium-intact tracheal preparation, cromakalim (1-100 micro M) significantly reduced the stimulation-induced (S-I) efflux of [3H]-acetylcholine from the radiolabelled, epithelium-denuded tracheal preparation in the lower flow chamber. In contrast, when the upper flow chamber contained an epithelium-denuded preparation, cromakalim (10 micro M) was without effect on the S-I efflux. Glibenclamide (1 micro M), an ATP-sensitive potassium channel blocker, was without effect on the S-I efflux when the upper chamber contained an unlabelled, epithelium-intact tracheal preparation. However, glibenclamide (1 micro M) prevented the inhibition of the S-I efflux by cromakalim (10 micro M). When the upper chamber contained an epithelium-intact tracheal preparation and the lower chamber contained an epithelium-denuded tracheal preparation, cromakalim (10 micro M), when infused through the side-arm of the T-piece, such that only the lower radiolabelled epithelium-denuded tracheal preparation was exposed to the drug, was without effect on the S-I efflux. The findings of the present study have provided evidence of an inhibitory action of the potassium channel opener cromakalim on transmitter acetylcholine release in rat trachea which is dependent on the functional integrity of the tracheal epithelium. The findings suggest that cromakalim may inhibit transmitter acetylcholine release by opening ATP-sensitive potassium channels, probably, on cells in the epithelial layer to release a putative epithelial factor, which in turn acts prejunctionally to mediate the inhibitory effect of cromakalim.

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