Halothane enhances exocytosis of [<sup>3</sup>H]‐acetylcholine without increasing calcium influx in rat brain cortical slices

Gomez, Renato Santiago; Prado, Marco A. M.; Carazza, Fernando; Gomez, Marcus V.

doi:10.1038/sj.bjp.0702603

Cited by 12 publications

(8 citation statements)

References 46 publications

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“…We observed that EGTA, Cd 2+ or TTX did not significantly affect the sevoflurane-induced [ 3 H]-ACh release. The data confirms our previous observation in which the volatile anesthetics halothane and isoflurane also causes an increase on the release of [ 3 H]-ACh that is independent of sodium and calcium channels but involves the mobilization of intracellular calcium stores (Gomez et al, 1999;Gomez et al, 2000). Indeed, we observed that BAPTA-AM, chelator of intracellular calcium stores, blocked the sevoflurane-induced release of [ 3 H]-ACh.…”

Section: Discussionsupporting

confidence: 93%

“…In an in vitro investigation, Bazil and Minneman (1989a,b) observed no effect of 1.25% halothane, 3% enflurane or 0.2% methoxyflurane on potassium-stimulated ACh release from rat cerebral cortex. It was also demonstrated that halothane did not inhibit the electrical-stimulated release of [ 3 H]-ACh from rat brain cortical slices, but it increased the basal release of [ 3 H]-ACh (Gomez et al, 1999) as well as isoflurane (Gomez et al, 2000). In addition, Taguchi et al (1991) observed that this volatile anesthetic increases ACh release from the midbrain interpeduncular nucleous of rats during anesthesia.…”

Section: Discussionmentioning

confidence: 90%

“…Indeed, we observed that BAPTA-AM, chelator of intracellular calcium stores, blocked the sevoflurane-induced release of [ 3 H]-ACh. It has been well documented that volatile anesthetics stimulate Ca 2+ release or leakage from either ryanodine-sensitive or IP 3 -sensitive stores in hippocampal and cerebrocortical (Kindler, 1999), rat brain cortical slices (Gomez et al, 1999;Gomez et al, 2000), transformed rat pituitary cell line (GH 3 ) (Hossain and Evers, 1994) and in a cholinergic cell line derived from the fusion of neuroblastome cell line with medial-septal neurons (SN56) (Gomez et al, 2001). In addition, it has been showed that isoflurane and sevoflurane affected presynaptic protein kinase C activity and the anesthetic effect on enzyme activation seems to be related to an increase in intracellular calcium concentration induced by these agents (Moe et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

“…It was shown that volatile anesthetics decreased the release of ACh in in vitro (Griffiths et al, 1995;Johnson and Hartzell, 1985) and in in vivo systems (Keifer et al, 1994;Shichino et al, 1997;Shichino et al, 1998). However, other studies reported an increase in the release of ACh by halothane (Gomez et al, 1999) and isoflurane from rat brain cortical slices (Gomez et al, 2000), and by halothane in rat striatal slices (Adachi et al, 2001). In addition, nitrous oxide and xenon, an inert gas that have anesthetic properties, also enhance the release of ACh in rat cerebral cortex in vivo (Shichino et al, 1998;Shichino et al, 2002).…”

Section: Introductionmentioning

confidence: 87%

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Acetylcholine Release Induced by the Volatile Anesthetic Sevoflurane in Rat Brain Cortical Slices

Silva

Gomez²,

Pinheiro

et al. 2005

Cell Mol Neurobiol

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1. We have investigated the effect of the volatile anesthetic sevoflurane on acetylcholine (ACh) release from rat brain cortical slices. 2. The release of [3H]-ACh into the incubation fluid was studied after labeling the tissue ACh with [methyl-3H]-choline chloride. 3. We observed that sevoflurane induced an increase on the release of ACh that was dependent on incubation time and anesthetic concentration. The sevoflurane-induced ACh release was not blocked by tetrodotoxin (TTX) and therefore was independent of sodium channels. In addition, the sevoflurane effect was not blocked by ethylene glycol-bis(beta-aminoethyl ether (EGTA) or cadmium (Cd2+), thus independent of extracellular calcium. 4. The sevoflurane-induced ACh release was inhibited by 1,2-bis (2-aminophenoxy) ethane-N,N,N',N'-tetra-acetic acid (BAPTA-AM), suggesting the involvement of intracellular calcium-sensitive stores in the process. Dantrolene, an inhibitor of ryanodine receptors, had no effect but 2-aminoethoxydiphenylborate (2-APB), a membrane-permeable inhibitor of inositol 1,4,5-triphosphate receptor inhibited the sevoflurane-induced release of ACh. 5. It is concluded that sevoflurane-induced release of ACh in brain cortical slices involves the mobilization of calcium from IP3-sensitive calcium stores.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 87%

See 2 more Smart Citations

Acetylcholine Release Induced by the Volatile Anesthetic Sevoflurane in Rat Brain Cortical Slices

Silva

Gomez²,

Pinheiro

et al. 2005

Cell Mol Neurobiol

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“…3 H]choline and monitored the release of labeled neurotransmitter as previously described (2,26,27,32). VAChT del/del mice are capable of producing ACh (see Fig.…”

Section: Resultsmentioning

confidence: 99%

The Vesicular Acetylcholine Transporter Is Required for Neuromuscular Development and Function

Castro

Jaeger

Martins-Silva

et al. 2009

Molecular and Cellular Biology

116

114

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The vesicular acetylcholine (ACh) transporter (VAChT) mediates ACh storage by synaptic vesicles. However, the VAChT-independent release of ACh is believed to be important during development. Here we generated VAChT knockout mice and tested the physiological relevance of the VAChT-independent release of ACh. Homozygous VAChT knockout mice died shortly after birth, indicating that VAChT-mediated storage of ACh is essential for life. Indeed, synaptosomes obtained from brains of homozygous knockouts were incapable of releasing ACh in response to depolarization. Surprisingly, electrophysiological recordings at the skeletalneuromuscular junction show that VAChT knockout mice present spontaneous miniature end-plate potentials with reduced amplitude and frequency, which are likely the result of a passive transport of ACh into synaptic vesicles. Interestingly, VAChT knockouts exhibit substantial increases in amounts of choline acetyltransferase, high-affinity choline transporter, and ACh. However, the development of the neuromuscular junction in these mice is severely affected. Mutant VAChT mice show increases in motoneuron and nerve terminal numbers. End plates are large, nerves exhibit abnormal sprouting, and muscle is necrotic. The abnormalities are similar to those of mice that cannot synthesize ACh due to a lack of choline acetyltransferase. Our results indicate that VAChT is essential to the normal development of motor neurons and the release of ACh.

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The Effects of Volatile Anesthetics on the Extracellular Accumulation of [3H]GABA in Rat Brain Cortical Slices

et al. 2013

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GABA is an inhibitory neurotransmitter that appears to be associated with the action of volatile anesthetics. These anesthetics potentiate GABA-induced postsynaptic currents by synaptic GABAA receptors, although recent evidence suggests that these agents also significantly affect extrasynaptic GABA receptors. However, the effect of volatile anesthetics on the extracellular concentration of GABA in the central nervous system has not been fully established. In the present study, rat brain cortical slices loaded with [(3)H]GABA were used to investigate the effect of halothane and sevoflurane on the extracellular accumulation of this neurotransmitter. The accumulation of [(3)H]GABA was significantly increased by sevoflurane (0.058, 0.11, 0.23, 0.46, and 0.93 mM) and halothane (0.006, 0.012, 0.024, 0.048, 0072, and 0.096 mM) with an EC50 of 0.26 mM and 35 μM, respectively. TTX (blocker of voltage-dependent Na(+) channels), EGTA (an extracellular Ca(2+) chelator) and BAPTA-AM (an intracellular Ca(2+) chelator) did not interfere with the accumulation of [(3)H]GABA induced by 0.23 mM sevoflurane and 0.048 mM halothane. SKF 89976A, a GABA transporter type 1 (GAT-1) inhibitor, reduced the sevoflurane- and halothane-induced increase in the accumulation of GABA by 57 and 63 %, respectively. Incubation of brain cortical slices at low temperature (17 °C), a condition that inhibits GAT function and reduces GABA release through reverse transport, reduced the sevoflurane- and halothane-induced increase in the accumulation of [(3)H]GABA by 82 and 75 %, respectively, relative to that at normal temperature (37 °C). Ouabain, a Na(+)/K(+) ATPase pump inhibitor, which is known to induce GABA release through reverse transport, abolished the sevoflurane and halothane effects on the accumulation of [(3)H]GABA. The effect of sevoflurane and halothane did not involve glial transporters because β-alanine, a blocker of GAT-2 and GAT-3, did not inhibit the effect of the anesthetics. In conclusion, the present study suggests that sevoflurane and halothane increase the accumulation of GABA by inducing the reverse transport of this neurotransmitter. Therefore, volatile anesthetics could interfere with neuronal excitability by increasing the action of GABA on synaptic and extrasynaptic GABA receptors.

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Halothane enhances exocytosis of [³H]‐acetylcholine without increasing calcium influx in rat brain cortical slices

Cited by 12 publications

References 46 publications

Acetylcholine Release Induced by the Volatile Anesthetic Sevoflurane in Rat Brain Cortical Slices

Acetylcholine Release Induced by the Volatile Anesthetic Sevoflurane in Rat Brain Cortical Slices

The Vesicular Acetylcholine Transporter Is Required for Neuromuscular Development and Function

The Effects of Volatile Anesthetics on the Extracellular Accumulation of [3H]GABA in Rat Brain Cortical Slices

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Halothane enhances exocytosis of [3H]‐acetylcholine without increasing calcium influx in rat brain cortical slices

Cited by 12 publications

References 46 publications

Acetylcholine Release Induced by the Volatile Anesthetic Sevoflurane in Rat Brain Cortical Slices

Acetylcholine Release Induced by the Volatile Anesthetic Sevoflurane in Rat Brain Cortical Slices

The Vesicular Acetylcholine Transporter Is Required for Neuromuscular Development and Function

The Effects of Volatile Anesthetics on the Extracellular Accumulation of [3H]GABA in Rat Brain Cortical Slices

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Halothane enhances exocytosis of [³H]‐acetylcholine without increasing calcium influx in rat brain cortical slices