Endogenous methyl palmitate modulates nicotinic receptor-mediated transmission in the superior cervical ganglion

Wen Lin Hung, Chao Zong Liu, Deshou Cao, Po Yi Chen, Mei Fang Chen, Shinn Zong Lin, Mansoor Mozayan, Alex F. Chen, Louis S. Premkumar, Donald S. Torry, Tony J.F. Lee

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Nitric oxide (NO) is identified as the endothelium-derived relaxing factor and a neurotransmitter with a superfusion bioassay cascade technique. By using a similar technique with rat superior cervical ganglion (SCG) as donor tissue and rabbit endothelium-denuded aortic ring as detector tissue, we report here that a vasodilator, which is more potent than NO, is released in the SCG upon field electrical stimulation (FES) or addition of nicotine. Release of this vasodilator was enhanced by arginine analogs, including Nω- nitro-L-arginine (a NO synthase inhibitor), suggesting that it is not NO. Analysis by gas chromatography/mass spectrometry identified 2 saturated fatty acids, palmitic acid methyl ester (PAME) and stearic acid methyl ester (SAME), being released from the SCG upon FES in the presence of arginine analogs. Exogenous PAME but not SAME induced significant aortic dilation (EC50 = 0.19 nM), indicating that PAME is the potent vasodilator. Release of PAME and SAME was significantly diminished in chronically decentralized SCG but not denervated SCG, suggesting the preganglionic origin. Furthermore, release of both fatty acids was calcium- and myosin light chain kinase-dependent, suggesting that both were released from axoplasmic vesicular stores. Electrophysiological studies further demonstrated that PAME but not SAME inhibited nicotine-induced inward currents in cultured SCG and the α7-nicotinic acetylcholine receptor-expressing Xenopus oocytes. Endogenous PAME appears to play a role in modulation of the autonomic ganglionic transmission and to complement the vasodilator effect of NO.

Original languageEnglish (US)
Pages (from-to)19526-19531
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number49
DOIs
StatePublished - Dec 9 2008

Keywords

  • Alpha7-nicotinic acetylcholine receptor
  • Fatty acid vasodilator
  • Palmitic and stearic acid methyl ester
  • Superfusion bioassay cascade

ASJC Scopus subject areas

  • General

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    Hung, W. L., Liu, C. Z., Cao, D., Chen, P. Y., Chen, M. F., Lin, S. Z., Mozayan, M., Chen, A. F., Premkumar, L. S., Torry, D. S., & Lee, T. J. F. (2008). Endogenous methyl palmitate modulates nicotinic receptor-mediated transmission in the superior cervical ganglion. Proceedings of the National Academy of Sciences of the United States of America, 105(49), 19526-19531. https://doi.org/10.1073/pnas.0810262105