Skip to main content
Log in

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

  • Published:
Cellular and Molecular Neurobiology Aims and scope Submit manuscript

Summary

  1. 1.

    We have investigated the effect of the volatile anesthetic sevoflurane on acetylcholine (ACh) release from rat brain cortical slices.

  2. 2.

    The release of [3H]-ACh into the incubation fluid was studied after labeling the tissue ACh with [methyl-3H]-choline chloride.

  3. 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(β-aminoethyl ether (EGTA) or cadmium (Cd2+), thus independent of extracellular calcium.

  4. 4.

    The sevoflurane-induced ACh release was inhibited by 1,2-bis (2-aminophenoxy) ethane-N,N,N’,N’-tetra-acetic acid (BAPTA-AM), suggestingthe 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. 5.

    It is concluded that sevoflurane-induced release of ACh in brain cortical slices involves the mobilization of calcium from IP_{3}-sensitive calcium stores.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Adachi, M., Ikemoto, Y., Kubo, K., and Takuma, C. (1992) Seizure-like movements during induction of anaesthesia with sevoflurane. Br. J. Anaesth. 68:214–215

    PubMed  Google Scholar 

  • Adachi, Y. U., Watanabe, H., Higuchi, T., Satoh, T., and Zsilla, G. (2001). Halothane enhances acetylcholine release by decreasing dopaminergic activity in rat striatal slices. Neurochem. Int. 40:189–193.

    Article  Google Scholar 

  • Adler, E. M., Augustine, G. J., Duffy S. N., and Chariton M. P. (1991). Alien intracellular calcium chelator attenuate neurotransmitter release at the squid giant synapse. J. Neurosci. 11:1496–1507.

    PubMed  Google Scholar 

  • Bazil, C. W., and Minneman, K. P. (1989a). Effects of clinically effective concentrations of halothane on adrenergic and cholinergic synapses in rat brain in vitro, J. Pharmacol. Exp. Ther. 248:143–148.

    Google Scholar 

  • Bazil, C. W., and Minneman, K. P. (1989b). Clinical concentrations of volatile anesthetics reduce depolarization-evoked release of [3H]-norepinephrine, but not [3H]-acetylcholine, from rat cerebral cortex. J. Neurochem. 53:962–965.

    Google Scholar 

  • Bertorelli, A., Hallstrom, A., Hurd, Y. L., Karlsson, S., Consolo, S., and Ungerstedt, U. (1990). Anaesthesia effects on in vivo acetylcholine transmission: Comparison of radioenzymatic and HPLC assays. Eur. J. Pharmacol. 175:79–83.

    Article  PubMed  Google Scholar 

  • Casali, T. A. A., Gomez, R. S., Moraes-Santos, T., Romano-Silva, M. A., Prado, M. A. M., and Gomez, M. V. (1997). Different effects of reducing agents on ω –conotoxin GVIA inhibition of [3H]-acetylcholine release from cortical slices and guinea-pig myenteric plexus. Br. J. Pharmacol. 120:88–92.

    PubMed  Google Scholar 

  • Fox, A. P., Nowycky, M. C., and Tsien R. W. (1987). Kinetic and pharmacological properties distinguishing three types of calcium currents in chick sensory neurons. J. Physiol. (Lond.) 394:149–172.

    Google Scholar 

  • Goldberg, A. M., and McCaman, R. E. (1973). The determination of picomole amounts of acetylcholine in mammalian brain. J. Neurochem. 20:1–8.

    PubMed  Google Scholar 

  • Gomez, R. S., Gomez, M. V., and Prado, M. A. M. (1996) Inhibition of Na+, K+,-ATPase by ouabain opens calcium channles coupled to acetylcholine release in guinea pig myenteric plexus. J. Neurochem. 66:1440–1447.

    PubMed  Google Scholar 

  • Gomez, R. S., Prado, M. A. M., Carazza, F., and Gomez, M. V. (1999). Halothane enhances exocytosis of [3H]-acetylcholine without increasing calcium influx in rat brain cortical slices. Br. J. Pharmacol. 127:679–684.

    Article  PubMed  Google Scholar 

  • Gomez, R. S., Gomez, M. V., and Prado, M. A. M. (2000). The effect of isoflurane on the release of [3H]-acetylcholine from rat brain cortical slices. Brain Res. Bull. 52:263–267.

    Article  PubMed  Google Scholar 

  • Gomez, R. S., Guatimosim, C., Barbosa, Jr. J., Massensini, A. R., Gomez, M. V., and Prado, M. A. M. (2001). Halothane induced intracellular calcium release in cholinergic cells. Brain Res. 921:106–114.

    Article  PubMed  Google Scholar 

  • Griffiths, R., Greiff, J. M. C., Haycock, J., Elton, C. D., Rowbotham, D. J., and Norman, R. I. (1995). Inhibition by halothane of potassium-stimulated acetylcholine release from rat cortical slices. Br. J. Pharmacol. 116:2310–2314.

    PubMed  Google Scholar 

  • Griffiths, R., and Norman, R. I. (1993). Effects of anaesthetics on uptake, synthesis and release of transmitters. Br. J. Anaesth. 71:96–107.

    PubMed  Google Scholar 

  • Hossain, M. D., and Evers, A. S. (1994). Volatile anesthetic-induced efflux of calcium from IP3-gated stores in clonal (GH3) pituitary cells. Anesthesiology 80:1379–1389.

    PubMed  Google Scholar 

  • Johnson, G. V. W., and Hartzell, C. R. (1985). Choline uptake, acetylcholine synthesis and release, and halothane effects in sinaptosomes. Anesth. Analg. 64:395–399.

    PubMed  Google Scholar 

  • Katsuoka, M., and Ohnishi, S. T. (1989). Inhalation anaesthetics decrease calcium content of cardiac sarcoplasmic reticulum. Br. J. Anaesth. 62:669–673.

    PubMed  Google Scholar 

  • Keifer, J. C., Baghdoyan, H. A., Becker, L., and Lydic, R. (1994). Halothane decreases pontine acetylcholine release and increased EEG spindles. Neuroreport 31:577–580.

    Google Scholar 

  • Kindler, C. H., Eilers, P., Donohoe, S., Ozer, S., and Bickler, P. E. (1999). Volatile anesthetics increase intracellular calcium in cerebrocortical and hippocampal neuron. Anesthesiology 90:1137–1145.

    Article  PubMed  Google Scholar 

  • Komatsu, H., Taie, S., Endo, S., Fukuda, K., Ueki, M., Nogaya, J., and Ogli, K. (1994). Electrical seizures during sevoflurane anesthesia in two pediatric patients with epilepsy. Anesthesiology 81:1535–1537.

    PubMed  Google Scholar 

  • Kudoh, A., and Matsuki, A. (2000). Sevoflurane stimulates inositol 1,4,5-triphosphate in skeletal muscle. An esth. Analg. 91:440–445.

    Google Scholar 

  • Lynch, C., and Frazer, M. J. (1994). Anesthetic alteration of ryanodine binding by cardiac calcium release channels. Biochim. Biophys. Acta. 1194:109–117.

    PubMed  Google Scholar 

  • Maruyama, S., Nakade, T., Kann, T., and Mikoshiba, K. (1997). 2-APB, 2- aminoethoxydiphenylborate, a membrane penetrable modulator of Ins(1,4,5)P3-induced Ca2+ release. J. Biochem. 122:495–505.

    Google Scholar 

  • Miller, M. S., and Gandolfi, A. J. (1979). A rapid, sensitive method for quantifying enflurane in whole blood. Anesthesiology 51:542–544.

    PubMed  Google Scholar 

  • Modica, P. A., Tempelhoff, R., and White, P. F. (1990). Pro- and anticonvulsant effects of anesthetics (part I). Anesth. Analg. 70:303–315.

    PubMed  Google Scholar 

  • Moe, M. C., Berg-Johnsen, J., Larsen, G. A., Kampenhaug, E. B., and Vinje, M. L. (2003). The effect of isoflurane and sevoflurane on cerebrocortical presynaptic Ca2+ and protein kinase C activity. J. Neurosurg. Anesthesiol. 15:209–214.

    Article  PubMed  Google Scholar 

  • Narahashi, J., Moore, J., and Scott, W. R. (1964). Tetrodotoxin blockage of sodium conductance increase in lobster giant axon. J. Gen. Phsyiol. 147:965–974.

    Article  Google Scholar 

  • Ohta, T., Ito, S., and Ohga, A. (1990). Inhibitory action of dantrolene on Ca-induced Ca2+ release from sarcoplasmic reticulum in guinea pig skeletal muscle. Eur. J. Pharmacol. 178:11–19.

    Article  PubMed  Google Scholar 

  • Peppiatt, C. M., Collins, T. J., Mackenzie, I., Conway, S. J., Holmes, A. B., Bootman, M. D., Berridge, M. J., Seo, J. T., and Roderick, H. L. (2003). 2-Aminoethoxydephenylborate (2-APB) antagonizes inositol 1,4,5-triphosphate-induced calcium release, inhibits calcium pumps and has a use-dependent and slowly reversible action on store-operated calcium entry channel. Cell Calcium 34:97–108.

    PubMed  Google Scholar 

  • Pocock, G., and Richards, C. D. (1996). Excitatory and inhibitory synaptic mechanism in anaesthesia. Br. J. Anaesth. 71:134–147.

    Google Scholar 

  • Prado, M. A. M., Gomez, M. V., and Collier, B. (1993). Mobilization of a vesamicol-insensitive pool of acetylcholine from a sympathetic ganglion by ouabain. J. Neurochem. 61:45–56.

    PubMed  Google Scholar 

  • Shichino, M. Murakawa, T., Adachi, T., Arai, Y., Miyazaki, Y., and Mori, K. (1998). Effects of inhalation anaesthetics on the release of acetylcholine in the rat cerebral cortex in vivo. Br. J. Anaesth. 80:365–370.

    PubMed  Google Scholar 

  • Shichino, T., Murakawa, T., Adachi, T., Arai, S., Nakao, T., Shinomura, J., Kurata, J., and Mori, K. (1997) Effects of isoflurane on in vivo release of acetylcholine in the rat cerebral cortex and striatum. Acta. Anaesthesiol. Scand. 41:1335–1340.

    PubMed  Google Scholar 

  • Shichino, M., Murakawa, T., Adachi, T., Arai, Y., Miyazaki, H., Segawa, H., Fukuda, K., and Mori, K. (2002). Effects of xenon on acetylcholine release in the rat cerebral cortex in vivo. Br. J. Anaesth. 88:866–868.

    Article  PubMed  Google Scholar 

  • Schotten, M., Greiser, V., Braun, V., Karlein, F., Schoendube, P., and Hanrath, P. (2001). Effect of volatile anesthetics on the force-frequency relation in human ventricular myocardium. Anesthesiology 95:1160–1168.

    Article  PubMed  Google Scholar 

  • Taguchi, K., Andresen, M. J., and Hentall, I. D. (1991). Acetylcholine release from the midbrain interpeduncular nucleous during anesthesia. Neuroreport 2:789–792.

    PubMed  Google Scholar 

  • Weldon, B. C., Bell, M., and Craddock, T. (2004). The effect of caudal analgesia on emergence agitation in children after sevoflurane versus halothane anesthesia. Anesth. Analg. 98:321–326.

    Article  PubMed  Google Scholar 

  • Wells, L. T., and Rasch, D. K. (1999). Emergence “delirium” after sevoflurane anesthesia: A paranoid delusion? Anesth. Analg. 88:1308–1310.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Marcus V. Gomez.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Silva, J.H., Gomez, R.S., Pinheiro, A.C.N. et al. Acetylcholine Release Induced by the Volatile Anesthetic Sevoflurane in Rat Brain Cortical Slices. Cell Mol Neurobiol 25, 807–818 (2005). https://doi.org/10.1007/s10571-005-4934-x

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10571-005-4934-x

Keywords

Navigation